\r\n\tEqually important are the consequences deriving from the extraordinary nature of the present times. The COVID-19 pandemic and the restrictive measures to contain the infection (lockdown and "physical distancing" in primis) have revolutionized the lives, and a distortion/modification of habits, rhythms, arrangements will continue to be necessary.
\r\n\tGovernments have implemented a series of actions to mitigate the spread of infections and alleviate the consequent pressure on the hospital system. On the other hand, the Covid-19 pandemic has caused a series of other cascading effects that will probably be much more difficult to mitigate and which expose to complex consequences. The past two years have brought many challenges, particularly for healthcare professionals, students, family members of COVID-19 patients, people with mental disorders, the frail, the elderly, and more generally those in disadvantaged socio-economic conditions, and workers whose livelihoods have been threatened. Indeed, the substantial economic impact of the pandemic may hinder progress towards economic growth as well as progress towards social inclusion and mental well-being.
\r\n\r\n\t
\r\n\tAlthough in all countries the knowledge on the impact of the pandemic on mental health is still limited and mostly derived from experiences only partially comparable to the current epidemic, such as those referring to the SARS or Ebola epidemics, it is likely that the demand for intervention it will increase significantly in the coming months and years. The extraordinary growth of scientific research in the field of neuroscience now offers the possibility of a new perspective on the relationship between mind and brain and generates new scenarios in understanding the long wave of the pandemic and in the prospects for treatment. Moreover, the pandemic also has led to opportunities to implement remote monitoring and management interventions.
\r\n\r\n\t
\r\n\tOverall this volume will address the complex relationship existing between COVID-19, mental health, acquired knowledge, and possible interventions taking a highly multidisciplinary approach; from physiological and psychobiological mechanisms, and neuromodulation through medical treatment, psychosocial interventions, and self-management.
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Introduction
Metabolic syndrome (MetS), known as syndrome X, Deadly Quartet, or insulin resistance syndrome is characterized by a cluster of metabolic risk factors such as obesity, hypertension, dyslipidemia, and elevated fasting plasma glucose [1]. The metabolic risk factors can result in type 2 diabetes (T2D) and cardiovascular disease (CVD) that are due to both genetic and environmental factors [2, 3]. For these reasons, MetS is becoming a global epidemic. The prevalence of MetS is estimated at 11.9–37.1% in Asia-Pacific region [4], 11.6–26.3% in Europe [5], and 22–24% in North America [6].
One of the primary mediators of MetS is known for insulin resistance (IR), which is a pathological state of improper cellular response to the hormone insulin in insulin-dependent cells such as skeletal muscle and adipose tissue [7]. IR is present in the majority of people with many metabolic disorders such as MetS and T2D. IR plays a crucial role in the pathophysiology of both T2D and CVD [7] but inversely related to insulin sensitivity in insulin-dependent tissues [8]. Clinical risk factors such as obesity, dyslipidemia, inflammation, hyperinsulinemia, and dysglycemia are also known to affect IR.
Although environmental factors such as lifestyle and socioeconomic status contribute to the development of IR and MetS, both IR and MetS are also being determined by genetic factors, as strongly evidenced by early familial genetic studies [9, 10, 11]. Based on these studies, advanced genetic analysis technologies such as genome-wide association studies (GWAS) and next-generation sequencing (NGS) are extensively being used to identify both common and rare genetic variants related to these metabolic disorder-associated traits.
This chapter is to present an overview of genetic variants involved in the pathogeneses of MetS and IR and to review the relevance between IR and MetS clusters in terms of genetic diversity.
2. Heritability of MetS and IR
The pieces of evidence for the heritability and co-occurrence of the metabolic traits have been revealed through early familial and twin genetic studies. The heritability of MetS, as defined by NCEP:ATPIII (National Cholesterol Education Program Adult Treatment Panel III) criteria, was estimated to be 24% (p = 0.006) in the Northern Manhattan Family Study, which was conducted in 803 subjects from 89 Caribbean-Hispanic families [9]. Each component of MetS has also an important genetic basis. The heritability was estimated at 46% for waist circumference (WC), 24% for fasting glucose, 60% for HDL-cholesterol, 47% for triacylglycerol (TAG), and 16% for systolic and 21% for diastolic blood pressure (BP). In the Linosa Study including 293 Caucasian native subjects from 51 families (123 parents and 170 offsprings), the heritability of MetS, as defined by NCEP:ATPIII, was estimated to be 27% (p = 0.0012) [12]. Among its components, the heritability for blood glucose and high-density lipoprotein (HDL)-cholesterol was 10% and 54%, respectively. The highest heritability was observed in the clustering of central obesity, hypertriglycemia, and low HDL-cholesterolemia (31%, p < 0.001). In an early study including 2508 adult male twin pairs, the accordance for the clustering of hypertension, diabetes, and obesity in the same individuals was 31.6% in monozygotic pairs and 6.3% in dizygotic pairs [13]. These early pieces of evidence have spurred many studies to find genetic determinants of MetS.
Although common genetic variants related to IR have been identified, these variants are known to make up only 25–44% of the heritability of IR [14, 15, 16]. For this reason, it is necessary to find low-frequency and rare genetic variations that affect the heritability of MetS and IR.
3. Genetic variants of MetS and IR
Significant progress has been made over the past decade to identify the genetic risk factors associated with the various traits of MetS. Although the complexity of MetS makes the identification of a genetic component of the disorder difficult, pieces of evidence for genetic determinants of MetS have been revealed through the linkage analysis approach, candidate gene association studies, GWAS, epigenetic studies, microRNAs, long-non-coding RNAs, system biological studies, and more recently NGS and whole-exome sequencing.
3.1 Linkage analysis approach
Many chromosomes and locus associated with MetS or its components or a combination of some of its components have been identified through linkage analysis. This approach has identified candidate quantitative trait loci (QTL). In 2209 subjects from 507 Caucasian families, a QTL associated with body mass index (BMI), WC, and fasting plasma insulin on chromosome 3q27 was identified, which includes genes such as the solute carrier family 2 of the facilitated glucose transporter (GLUT2) [17].
In a study including 456 Caucasian (white) and 217 African-American (black) subjects from 204 families, evidence of linkage for increased body fat, abdominal visceral fat, TAG, fasting glucose, fasting plasma insulin, blood pressure, and decreased HDL-cholesterol was identified on chromosome 10p11.2 and 19q13.4 and 10q13.4 in white [18]. In black subjects, the linkage was identified on chromosome 1p34.1 [18].
In a study including four ethnic groups (Caucasian, Mexican-American, African-American, and Japanese-American), evidence of linkage of MetS traits (weight/waist, lipid factor, and BP) was identified, where there is a strong linkage on chromosome 2q12.1-2q12 for Caucasian subjects and 3q26.1-3q29 for Mexican-American subjects [19].
Genetic data were obtained for 2467 subjects from 387 three-generation families and 1082 subjects from 256 sibships, where a genomic region on chromosome 2 included a pleiotropic locus contributing to the clustering of multiple metabolic syndrome (MMS)-related phenotypes (BMI, waist-to-hip ratio (WHR), subscapular skinfold, TAG, HDL-cholesterol, homeostasis model assessment (HOMA) index, plasminogen activator inhibitor-1-antigen, and serum uric acid) [20].
In a study including 250 German families, a genome-wide linkage scan for T2D supports the existence of MetS locus on chromosome 1p36.13 and T2D locus on chromosome 16p12.2 [21].
In a study with 715 individuals in 39 low-income Mexican American families, strong evidence of a major locus near markers D1S1597 and D1S407 on chromosome 1p36.21 that influences variation in symptomatic or clinical gallbladder disease through a genome-scan and linkage approach was revealed [22].
3.2 Candidate gene association studies
Candidate gene association studies identify and investigate many candidate genes that regulate biological processes related to MetS. Analysis of the mutation burden of candidate genes is among the first methods used to uncover MetS genes. Especially, the association of MetS and single nucleotide polymorphisms (SNPs) in related genes has been examined in many studies.
An association with MetS for 8 SNPs that are mostly in 25 genes involved in lipid metabolism was revealed in 88 studies with 4000 subjects. In these studies, the minor allele of C56G (APOA5), T1131C (APOA5), rs9939609 (FTO), C455T (APOC3), rs7903146 (TCF7L2), C482T (APOC3), and 174G > C (IL6) were more prevalent in subjects with MetS but the minor allele of Taq-1B (CETP) was less prevalent in those [23].
The association of HSD11B1 variants and HSD11B1 expression in abdominal adipose tissue with T2D, MetS, and obesity was identified in 802 studies. Especially, a polymorphic variant was identified to be related to T2D in a study including Pima Indians, and an association between MetS with another polymorphic variant at the HSD11B1 gene was identified in an Indian study. However, most studies did not find an association between HSD11B1 polymorphic variants and T2D, MetS, and obesity, suggesting that the variants may play a minor role to develop obesity, T2D, and MetS [24].
A meta-analysis study including 25 reports revealed an association of ADIPOQ rs2241766 and rs266729 polymorphisms with MetS in the Chinese population, where the G allele of rs2241766 increased the risk of MetS but no relevance to rs266729 was found [25].
In a study including 442 adults with MetS, it was revealed that APOE genotype affected IR, apolipoprotein (apo) CII, and CIII depending on plasma fatty acid (FA) levels in MetS. Elevated n-3 polyunsaturated FA (PUFA) was related to lower concentration of apo CIII in E2 carriers and elevated C16:0 was related to IR in E4 carriers. Decreased long-chain n-3 PUFA was associated with reduced apo CII level in E2 carriers, after FA intervention. These results suggest that subjects with MetS may benefit from personalized dietary interventions based on APOE genotype [26].
A meta- and gene-based analysis including 18 studies was carried out to investigate the association of fat mass and obesity-related FTO gene polymorphisms with MetS, suggesting that FTO is strongly related to MetS (p < 10−5) [27].
BALB/c mice are known to be resistant to a high-fat diet (HFD)-induced obesity. A recent study demonstrated that Nod2−/−BALB/c mice developed HFD-dependent obesity and risk factors of MetS such as hyperglycemia and hyperlipidemia. Interestingly, Nod2−/− HFD mice showed changes in the composition of gut flora and also delivered sensitivity to hyperglycemia, steatosis, and weight gain to wild type germ-free mice. Therefore, these results suggest that not only Nod2 plays a novel role in obesity but also that Nod2 and Nod2-regulated gut flora protect BALB/c mice from diet-induced obesity and metabolic disorders [28].
More recently, a multiple-genotype and multiple-phenotype analysis of a gene-based SNP set has been performed to identify new susceptible variants associated with MetS in 10,049 Korean individuals [29]. In this study, 27 SNP pairs were associated with MetS in the discovery stage and also replicated. Of these SNPs, 3 SNP pairs in each SIDT2, UBASH3B, and CUX2 gene were significant in the multiple-SNP and multiple-phenotype analysis rather than in the single-SNP and multiple-phenotype analysis. Especially, an association of MetS with an intronic SNP pair, rs7107152 (p = 3.89 × 10−14) and rs1242229 (p = 3.64 × 10−13), in SIDT2 gene at 11q23.3 was found. These 2 SNPs are also associated with the expression of SIDT2 and TAGLN that promote insulin secretion and lipid metabolism, respectively. These results suggest the usefulness of the multiple-genotype and multiple-phenotype analysis platform to identify new genetic loci in complex metabolic disorders such as MetS.
Although candidate genetic association studies have reported many genetic variations associated with MetS, often these results have not been replicated in other populations and been identified through GWAS. These examples include polymorphisms in or near genes encoding GAD2, ENPP1, and SCL6A14. Moreover, most of the identified genes underlie only one MetS trait. Few exceptions contain mutations in ADIPOQ related to hypertension, T2D, and dyslipidemia. Other examples contain mutations in FOXC2, SREBP1, NR3C1, and GNB3 genes.
3.3 GWAS
GWA studies are an approach used to analyze an association of SNPs in subjects with MetS or IR and to date, being carried out by many researchers.
3.3.1 Genetic diversity of MetS
Over the past 10 years, GWAS have identified many genetic variants associated with each trait of MetS. Many genetic loci associated with lipid levels were discovered and refined by GWAS which identified 157 loci related to lipid levels at p < 5 x 10−8, including 62 loci not previously related to lipid levels [30]. Among the loci, 39 loci were associated with TAG levels and 71 with HDL-cholesterol. Several loci associated with each component of MetS have pleiotropic effects on two or more traits related to MetS.
A GWA meta-analysis including 76,150 subjects showed that the rs2943634 variant near IRS1 was associated with an elevated visceral to subcutaneous fat ratio, IR, dyslipidemia (higher TAG and lower HDL-cholesterol), risk of T2D, and reduced adiponectin levels [31]. Genetic variants in the GCKR gene were linked to fasting glucose levels [32], TAG [33], and non-alcoholic fatty liver disease [34]. Variants for obesity in/near FTO and MC4R genes were associated with specific measures of adiposity such as WC [35], HDL-cholesterol levels [30], IR [36, 37], and risk of T2D [35]. Variants in the GRB14 gene were also linked to BMI-adjusted WHR [38], T2D [39], and fasting insulin levels.
In a GWAS comparing T2D subjects (n = 1924) and control (n = 2938) for autosomal SNPs (n = 490,032), SNPs in FTO gene region on chromosome 16 were identified to be strongly associated with T2D (e.g., rs9939609, OR = 1.27, p = 5 × 10−8). This strong association was furthermore reproduced by analyzing SNP rs9939609 in T2D subjects (n = 3757) and controls (n = 5346) (OR = 1.15, p = 9 × 10−6) [35]. However, some of these variants were also associated with MetS, suggesting that genes such as FTO, MC4R, and IRS1 play important roles in the progression of MetS [40]. Especially, among several obesity-related loci found to be related to MetS-related traits in the GWAS studies, FTO and MC4R genes are considered to be the strongest candidates for body weight control, and IRS1 is known to have an important effect on IR. These results may provide valuable information to understand the role of genetic control of adiposity and IR in the development of MetS.
GWA studies of MetS as a whole or a combination of its traits have also identified a number of both common and rare genetic variants. A GWA study was conducted to identify common genetic variants of MetS and its related components in 4560 Indian Asian men with a high prevalence of these conditions. In this study, no genetic variation showed an association with MetS as a whole. However, several variations were related to single components. Especially, 2 SNPs near CETP, 2 at 8p21.3 near LPL, 2 at 11q12.2 near FADS1 and FADS2, and 1 at 21q22.3 near FLJ41733 associated with HDL-cholesterol (p < 10−6), and 1 SNP near TCF7L2 associated with T2D (p < 10−6) were identified [41].
A study by the STAMPEDE Consortium included 13 independent studies, comprising a total of 22,161 subjects of European ancestry, was conducted to find genetic determinants contributing to the correlated architecture of MetS traits, using MetS as a whole or pairs of its components as phenotypes [42]. In this study, the 5 SNPs in LPL, APOA5 cluster (ZNF259, BUD13, and APOA5), and CETP genes were found to be associated with MetS. Especially, a total of 27 genetic variants in or near 16 genes were associated with bivariate combinations of 5 MetS traits, including variants in LIPC (chromosome 15q21-q23) associated with HDL-cholesterol-fasting glucose (rs2043085, p = 1.3 x 10−8) and with WC-HDL-cholesterol (rs10468017, p = 5.5 x 10−8), ABCB11 (chromosome 2q24) associated with HDL-cholesterol-fasting glucose (rs569805, p = 8.5 x 10−8) and with HDL-cholesterol-TAG (rs2954026, p = 7.9 x 10−9), TRIB1 (chromosome 8q24.13) associated with TAG-BP (rs2954033, p = 8.5 x 10−9), TFAP2B (chromosome 6p12) associated with WC-fasting glucose (rs2206277, p = 1.3 x 10−7), LOC100128354 (chromosome 11q21) and MTNR1B associated with BP-fasting glucose (rs1387153, p = 8.1 x 10−9), HDL-cholesterol-fasting glucose (rs1387153, p = 2.4 x 10−9), and TAG-fasting glucose (rs10830956, p = 4.8 x 10−11), LOC100129500 (chromosome 19q13.2) associated with HDL-cholesterol-TAG (rs439401, p = 1.0 x 10−8), and LOC100129150 variants with HDL-cholesterol-TAG (rs9987289, p = 1.1 x 10−8) and HDL-cholesterol-WC (rs9987289, p = 3.7 x 10−8) [42]. These common genetic variations can partly explain the covariation in the MetS traits.
In a study for susceptibility loci associated with MetS and its traits was conducted in four Finnish cohorts consisting of 2637 MetS cases and 7927 controls. One genetic variant (rs964184) in A APOA1/C3/A4/A5 gene cluster region on chromosome 11, known as lipid locus was found to be associated with MetS in all 4 study samples (p = 7.23 × 10−9 in meta-analysis) and significantly associated with several very low-density lipoprotein (VLDL), TAG, and HDL metabolites (p = 0.024–1.88 × 10−5). Several genetic variants in or near 4 known loci related to lipids (LPL, CEPT, APOA1/C3/A4/A5, and APOB) were strongly associated with TAG/HDL/WC factors [43], but none was associated with 2 or more uncorrelated MetS traits. A polygenetic risk score (PRS), which was calculated as the number of alleles in loci associated with individual MetS traits, was significantly associated with MetS traits. These results suggest that genes associated with lipid metabolism pathways have crucial roles in the development of MetS. However, in this study, little evidence for pleiotropy associating obesity and dyslipidemia with the other MetS traits (hyperglycemia and hypertension) was found.
Genetic loci associated with the clustering of 6 MetS-related phenotypes (atherogenic dyslipidemia, vascular dysfunction, vascular inflammation, pro-thrombotic state, central obesity, and elevated plasma glucose) including 19 quantitative traits were identified by GWAS in 19,486 European American and 6287 African American Candidate Gene Association Resource Consortium participants [44]. In this study, 606 significant SNPs in and near 19 loci (p = 2.13 x 10−7) were identified in European Americans. Many of these loci were associated with at least one MetS-related trait domain and consistent with results in African Americans. Three new pleiotropic loci in or near APOC1, BRAP, and PLCG1, which were associated with multiple phenotype domains were identified. Several loci previously identified by GWAS for each trait of MetS, including LPL, ABCA1, and GCKR, were also associated with at least 2 trait domains. These results support the presence of genetic variants with pleiotropic effects on adiposity, inflammation, glucose regulation, dyslipidemia, vascular dysfunction, and thrombosis. Such loci could apply to uncover metabolic dysregulation and identify targets for early intervention.
3.3.2 Genetic diversity of IR
To date, many of the loci related to risks of developing IR have been identified and found to be associated with measures such as insulin sensitivity and secretion.
In an early meta-analysis, genetic variants related to IR were identified in 21 cohorts consisting of a non-diabetic group, which includes 46,186 subjects with measures of fasting glucose and 38,238 subjects with measures of fasting glucose and HOMA-IR. In additional 76,558 subjects, 25 SNPs were followed up with this approach, identifying 16 loci related to fasting glucose and 2 loci related to fasting insulin. In this study, several loci near GCKR including a new locus near IGF1 were found to be associated with IR [32]. These results were replicated in a further 14 cohorts, which included 29,084 non-diabetic subjects with measures of fasting proinsulin, insulin secretion, and sensitivity [45]. Association of 37 risk loci for T2D with measures of insulin secretion, sensitivity, and processing and clearance was examined in 58,614 non-diabetic subjects and 17,327 subjects with measures of glycemic traits, revealing that the risk loci were grouped into 5 major categories including one cluster with 4 loci (PPARG, KLF14, IRS1, and GCKR) associated with IR [46].
A joint meta-analysis (JMA) approach has been developed to identify genetic variants associated with either fasting glucose and/or fasting insulin. This approach identified 6 loci that include 5 new variants associated with levels of fasting insulin (IRS1, COBLL1-GRB14, PPP1R3B, PDGFC, UHRF1BP1, and LYPLAL1) [47].
A large-scale meta-analysis including 133,010 subjects identified 17 loci significantly associated with fasting insulin. These loci included genes associated with other metabolic traits (FTO, TCF7L2, PPARG, ARL15, RSPO3, and ANKRD55-MAP3K1) and newly identified loci (YSK4, FAM13A, TET2, PEPD, and HIP1) [48]. In 2 further studies, these loci were used to make an IR PRS identify the relationship between variants associated with fasting insulin and the risk of each individual developing IR and T2D [49, 50]. The 2 studies identified that the IR GRSs were associated with decreased insulin sensitivity and lower BMI. In one of these 2 studies, a PRS was generated from 10 genetic loci that were related to lower HDL-cholesterol and higher TAG (PPARG, IRS1, GRB14, PEPD, FAM13A1, PDGFC, LYPLAL1, RSPO3, ARL15, and ANKRD55-MAP3K1) [49]. In the other study, 19 loci were used to generate their IR PGS and 11 risk variants were identified to be related to increased TAG and lower HDL-cholesterol along with a lower BMI [50]. In these studies, IR PRSs were used to highlight that IR can develop without obesity and high BMI.
IRS1 is a signaling adapter protein that is encoded by the IRS1 gene in humans and a key factor of the insulin signaling pathway initiating the activation of phosphoinositide 3-kinase (PI3K) in response to insulin. The C allele at the SNP (rs2943641) near the IRS1 gene was found to be associated with IR and hyperinsulinemia in a European population. Through functional studies, the risk allele was found to be associated with lower levels of basal IRS1 protein and decreased PI3K activity during insulin infusion, indicating a causative role for the genetic variant on risk of IR [51]. The SNP (rs2943650) near IRS1 was also associated with lower HDL-cholesterol, elevated TAG, IR, and lower body fat percentage [31]. Significant associations of the variants in FTO with fasting insulin and insulin sensitivity were identified [37]. The risk variant in or near TCF7L2 was found to be associated with both impaired β-cell function and IR [52]. A variant in NAT2 was also found to be associated with a measure of insulin sensitivity in four European cohorts of 2764 non-diabetic individuals [53], supporting a role for NAT2 in insulin sensitivity. In this study, a variant of NAT2 was found to be strongly associated with reduced insulin sensitivity that was independent of BMI. The A allele at the SNP (rs1208) was significantly associated with IR-related traits, including increased fasting glucose, total cholesterol and LDL-cholesterol, hemoglobin A1C (HbA1c), TAG, and coronary artery disease (CHD). IGF1 is functionally similar to insulin and controls growth and development. Lower levels of IGF1 were found to be associated with decreased insulin sensitivity [54], and the SNP (rs35767) in the IGF1 gene suggested that the G allele has lower levels of IGF-1 compared to the A allele [55].
In a GWA study of a UK cohort of Indian-Asian and European ancestry, MC4R was found to be associated with both IR with measures of HOMA-IR and WC, and with higher frequencies of risk alleles found in the Indian-Asian cohort [36].
In a GWA study of a cohort with Indian ancestry, 2 loci near TMEM163 were found to be associated with both reduced plasma insulin and HOMA-IR [56].
In a GWA study of an African-American cohort, the SNP (rs7077836) near TCERG1L and the SNP (rs17046216) in SC4MOL were found to be associated with both fasting insulin and HOMA-IR [57]. ARL15 belongs to a family of intracellular vesicle trafficking, and its exact function remains unknown. However, variants in ARL15 were found to be associated with decreased levels of adiponectin and risk of T2D, CHD, and IR as measured by HOMA-IR [58].
To date, approximately 60 loci related to the risk of IR have been identified through GWAS, and among them, the top 10 IR-related loci have been replicated in 2 GWA studies [48, 59]. They are in and near the noncoding regions of IRS1 (rs2943645), PPARG (rs17036328), GRB14 (rs10195252), PEPD (rs731839), PDGFC (rs6822892), MAP3K1 (rs459193), ARL15 (rs4865796), FAM13A (rs3822072), RSPO3 (rs2745353) and LYPLAL1 (rs4846565). The PRS including the risk alleles of the 10 loci was associated with the cardiometabolic phenotypes such as lower BMI, lower body fat percentage, smaller hip circumference, and decreased leg fat mass as well as the risk phenotypes such as higher fasting insulin and higher TAG levels. These results suggest that limited storage capacity of subcutaneous adipose tissue (SAT) and consequently the elevation of ectopic fat deposition may be associated with the genetic link with IR [48, 49].
3.4 Low-frequency and rare variants
Whole-genome and exome sequencing approaches as relatively new genetic analysis technologies are being used to pinpoint the effects of minor allele frequencies (MAF ≤ 5%) and rare variants (MAF ≤ 0.5%) on the heritability of metabolic disorders such as MetS and IR.
The genomes of 1092 individuals from 14 populations were analyzed by using both the whole-genome and exome sequencing methods to identify low-frequency and rare genetic variants across 14 populations in the 1000 Genome Project [60]. The reference panels gained from this project can capture up to 98% accessible SNPs at a frequency of 1% in related populations and also enable researchers to analyze common and low-frequency variants in each individual from various populations. The 38 million SNP panels from the 1000 Genomes Project gave near complete coverage of common and low-frequency genetic variation with MAF ≥0.5% across European ancestry populations.
The European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium carried out 22 GWAS to examine associations of genetic variants with WHR, fasting glucose, BMI, and fasting insulin in 87,048 individuals of European ancestry. This study identified two new loci for BMI, and fasting glucose and new lead SNPs at 29 loci including the SNP (rs1260326) near GCKR for fasting insulin [61].
Whole exome sequencing in a Danish cohort of 1000 individuals with T2D, BMI >27.5 kg/m2, and hypertension and of 1000 controls identified 70,182 SNPs with MAF > 1%. Subsequent exome sequencing was performed in a two-stage follow-up in 15,989 Danes and a further 63,896 Europeans. This study showed associations of two common SNPs in COBLL1 (MAF = 12.5%, OR = 0.88, p = 1.2 × 10−11) and MACF1 (MAF = 23.4%, OR = 1.10, p = 8.2 × 10−10) with T2D and a low frequency variant in CD300LG (MAF = 3.5%, p = 8.5 × 10−14) with fasting HDL-cholesterol [62].
Although physiological functions of risk variants in COBLL1 and MACF1 remain still unclear, a risk variant rs72836561 at CD300LG was found to be associated with the decreased mRNA expression level of CD300LG in both skeletal muscle and adipose tissue, elevated intramyocellular lipid, and decreased insulin sensitivity, through a functional study. These results suggest an association between this variant and MetS traits [63].
Exome sequencing in an Icelandic population revealed that a low-frequency (1.47%) variant (rs76895963) in CCND2 decreased the risk of T2D (OR = 0.53, p = 5.0 × 10−21) and was associated with elevated CCND2 expression [64]. However, this variant was also associated with both greater height and higher BMI (1.17 cm per allele, p = 5.5 × 10−12 and 0.56 kg/m2 per allele, p = 6.5 × 10−7, respectively).
In 2733 individuals from the Greenlandic population that were historically isolated, combination analyses of Cardio-Metabochip based genotyping and exome sequencing revealed that a common variant in TBC1D4 was associated with higher fasting glucose and decreased insulin sensitivity, resulting in decreased insulin-stimulated glucose uptake due to the variant [65].
Recently, whole-genome sequencing in a UK10K-cohort project consisting of 3781 healthy individuals with exome sequencing of 6000 individuals with either rare disease, severe obesity, or neurodevelopmental disorders has been performed to identify low-frequency and rare variants [66]. This project identified 24 million novel genetic variants including novel alleles associated with levels of TAG (APOB), adiponectin (ADIPOQ), and LDL-cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests and provided reference panels with increased coverage of low-frequency and rare variants. These panels are now being used to identify associations of low-frequency and rare variants with various traits related to health and disease.
3.5 Epigenetic determinants
Fatty acid-binding proteins (FABPs) play important roles in lipid metabolism and signaling. Dyslipidemia often occurs along with IR, obesity, and hypertension in individuals with MetS. The methylation status of CpG islands of a key regulator of lipid homeostasis, FABP3, is known as a quantitative trait associated with MetS phenotypes in humans. To identify if CpG methylation of FABP3 affects MetS traits in 517 Northern European family populations, the CpG islands in the FABP3 gene were profiled by a quantitative methylation analysis method. In this study, regional methylation was found to be strongly associated with plasma total cholesterol (p = 0.00028) and associated with LDL-cholesterol (p = 0.00495) [67]. Methylation at individual units was significantly associated with MetS traits such as insulin sensitivity and diastolic BP (p < 0.0028). These results suggest that DNA methylation of FABP3 strongly affects MetS and might have important implications for insulin, lipids, and cardiovascular phenotypes of MetS.
Meanwhile, malnutrition in childhood, infancy, or fetus affects the prevalence of MetS in adults and their offspring [68], suggesting that maternal malnutrition affects gene expression in offspring through epigenetic mechanisms.
To date, most studies examining epigenetic changes related to MetS or IR have been conducted in animals and few studies have been conducted in humans. Therefore, further studies in humans are needed in the future.
4. CRISPR screen for genes affecting MetS or IR
Although many GWA studies are widely used to identify genetic loci associated with IR, it remains challenging to identify the causal gene in each locus [69]. Recently, structural and functional connections between GWAS loci and vicinal or distal genes were identified by chromosome conformation capture (3C) technology and expression quantitative trait loci (eQTL) studies [70, 71]. However, the 3C experiments are expensive and the eQTL studies cannot identify all the causal genes for a locus. Moreover, the 2 methods cannot pinpoint the causal genes and mechanisms related to the risk loci of IR. More recently, clustered regularly interspaced short palindromic repeats (CRISPR) knockout screening platform as an alternative method has been applied to pinpoint functions of new candidate causal genes at IR-associated loci in human preadipocytes and adipocytes [72]. This screening platform successfully characterized the functions of 10 new candidate causal genes at IR-associated loci. The 10 candidate genes (PPARG, IRS-1, FST, PEPD, PDGFC, MAP3K1, GRB14, ARL15, ANKRD55, and RSPO3) showed diverse phenotypes in the 3 insulin-sensitizing mechanisms, including lipid metabolism, adipogenesis, and insulin signaling, and the first 7 of these genes could affect all the 3 mechanisms. Additionally, 5 of 6 eQTL genes were identified as the top candidate causal genes (IRS-1, GRB14, FST, PEPD, and PDGFC), and expression levels of these 5 genes in human subcutaneous adipose tissue were found to be associated with increased risk of IR. Interestingly, it was first revealed in this study that the FST, PEPD, and PDGFC are involved in the functions of adipose in IR. Despite these findings, little is known about other functions of these 3 genes in adipose tissue, which may include novel molecular mechanisms for cardiometabolic disease. In this regard, studies will be needed to uncover new functions of these 3 genes in adipose tissue.
5. Conclusions
MetS and IR are central risk factors for the development of dyslipidemia, T2D, and CVD as well as complex metabolic traits. Many of the genetic variations implicated in the development of the MetS and IR are associated with glucose and lipid metabolism, respectively. Significant progress has been made in the identification of common and rare genetic variations associated with the MetS and IR in different populations, driven by the advent of GWAS and more recently, genome and exome sequencing approaches.
Despite many scientific efforts in identifying many genetic loci associated with the MetS and IR, their exact molecular pathogenesis remains unclear. Further studies are needed to identify functional links between the genetic variants and the phenotypes and subsequently to uncover the underlying molecular mechanisms of both metabolic disorders.
Clinical validation of the variants identified by several genetic analysis approaches is challenging for reasons resulting from implications by an individual’s lifestyle and environmental factors as well as by genetic factors. In this aspect, studies including larger and more homogeneous populations are needed to identify genetic variants that underlie the association of the various traits of MetS and/or IR. However, results obtained from these studies should be replicated in different populations with a sufficient sample size to avoid false-positive associations and to reduce systematic biases and technical errors.
Approaches such as CRISPR, 3C, and eQTL are being used to identify structural and functional associations between genetic loci discovered by GWAS or exome sequencing and regional or distal genes. Among them, CRISPR as an in vitro screening platform may be used effectively to pinpoint causal genes at loci associated with MetS and IR in the near future. Currently, MetS and IR have been becoming a health and financial burden worldwide. The exact identification of validated variants that affect the MetS and IR might provide new preventive and treating strategies for the 2 metabolic disorders and related diseases.
\n',keywords:"metabolic disorders, genetic variation, genetic biomarker, genetic analysis",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73378.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73378.xml",downloadPdfUrl:"/chapter/pdf-download/73378",previewPdfUrl:"/chapter/pdf-preview/73378",totalDownloads:332,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:1,totalAltmetricsMentions:0,impactScore:0,impactScorePercentile:41,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"July 2nd 2020",dateReviewed:"September 7th 2020",datePrePublished:"October 12th 2020",datePublished:"May 19th 2021",dateFinished:"September 29th 2020",readingETA:"0",abstract:"A key in the etiology of a cluster of metabolic syndrome such as hyperglycemia, dyslipidemia, and obesity is known for insulin resistance, which is becoming a major global public health problem. Extensive studies have revealed many genetic factors for both insulin resistance and the components of metabolic syndrome. Advanced modern genotyping methods including genome-wide association studies and next-generation sequencing have allowed for the identification of both common and rare genetic variants related to these chronic disease-associated traits. Multiple genotype–phenotype studies are also needed to identify new and accurate genetic biomarkers in these conditions. The purpose of this chapter is to present genetic variants related to the pathogenesis of metabolic syndrome and insulin resistance and is to review the relevance between insulin resistance and metabolic syndrome clusters in terms of genetic diversity.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73378",risUrl:"/chapter/ris/73378",book:{id:"9743",slug:"genetic-variation"},signatures:"Sanghoo Lee, Jinwoo Ahn, Jimyeong Park, Hyeonkyun Na, Youngkee Lee, Yejin Kim, Gayeon Hong and Kyoung-Ryul Lee",authors:[{id:"326192",title:"Ph.D.",name:"Sanghoo",middleName:null,surname:"Lee",fullName:"Sanghoo Lee",slug:"sanghoo-lee",email:"sprout30@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"326442",title:"Dr.",name:"Kyoung-Ryul",middleName:null,surname:"Lee",fullName:"Kyoung-Ryul Lee",slug:"kyoung-ryul-lee",email:"dkrlee@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"329806",title:"Mr.",name:"Jinwoo",middleName:null,surname:"Ahn",fullName:"Jinwoo Ahn",slug:"jinwoo-ahn",email:"jinwoo_ahn@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"329808",title:"Ms.",name:"Jimyeong",middleName:null,surname:"Park",fullName:"Jimyeong Park",slug:"jimyeong-park",email:"jimyeong@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"329809",title:"MSc.",name:"Hyeonkyun",middleName:null,surname:"Na",fullName:"Hyeonkyun Na",slug:"hyeonkyun-na",email:"hyeonkyun_na@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"329810",title:"BSc.",name:"Youngkee",middleName:null,surname:"Lee",fullName:"Youngkee Lee",slug:"youngkee-lee",email:"youngkee_lee@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"329811",title:"MSc.",name:"Yejin",middleName:null,surname:"Kim",fullName:"Yejin Kim",slug:"yejin-kim",email:"yejin_kim@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"329812",title:"BSc.",name:"Gayeon",middleName:null,surname:"Hong",fullName:"Gayeon Hong",slug:"gayeon-hong",email:"gayeon_hong@scllab.co.kr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Heritability of MetS and IR",level:"1"},{id:"sec_3",title:"3. Genetic variants of MetS and IR",level:"1"},{id:"sec_3_2",title:"3.1 Linkage analysis approach",level:"2"},{id:"sec_4_2",title:"3.2 Candidate gene association studies",level:"2"},{id:"sec_5_2",title:"3.3 GWAS",level:"2"},{id:"sec_5_3",title:"3.3.1 Genetic diversity of MetS",level:"3"},{id:"sec_6_3",title:"3.3.2 Genetic diversity of IR",level:"3"},{id:"sec_8_2",title:"3.4 Low-frequency and rare variants",level:"2"},{id:"sec_9_2",title:"3.5 Epigenetic determinants",level:"2"},{id:"sec_11",title:"4. CRISPR screen for genes affecting MetS or IR",level:"1"},{id:"sec_12",title:"5. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'[Third report of the National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, ad treatment of high blood cholesterol in adults (adult treatment panel III) final report. 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Detailed physiologic characterization reveals diverse mechanisms for novel genetic loci regulating glucose and insulin metabolism in humans. Diabetes. 2010;59(5):1266-75]'},{id:"B46",body:'[Dimas AS, Lagou V, Barker A, et al. Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes. 2014;63:2158-71]'},{id:"B47",body:'[Manning AK, HivertMF, Scott RA, et al. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet. 2012;44(6):659-69]'},{id:"B48",body:'[Scott RA, Lagou V, Welch RP, et al. DIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012;44:991-1005]'},{id:"B49",body:'[Scott RA, Fall T, Pasko D, et al. 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Diabetologia. 2013;56(2):298-310]'},{id:"B63",body:'[Støy J, Kampmann U, Mengel A, et al. Reduced CD300LG mRNA tissue expression, increased intramyocellular lipid content and impaired glucose metabolism in healthy male carriers of Arg82Cys in CD300LG: a novel genometabolic cross-link between CD300LG and common metabolic phenotypes. BMJ Open Diab Res Care. 2015;3(1):e000095]'},{id:"B64",body:'[Steinthorsdottir V, Thorleifsson G, Sulem P, et al. Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nat Genet. 2014;46(3):294-8]'},{id:"B65",body:'[Moltke I, Grarup N, Jørgensen ME, et al. A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature. 2014;512(7513):190-3]'},{id:"B66",body:'[UK10K Consortium; Walter K, Min JL, Huang J, et al. The UK10K project identifies rare variants in health and disease. Nature. 2015;526(7571): 82-90]'},{id:"B67",body:'[Zhang Y, Kent JW, Lee A, Cerjak D, et al. Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a Northern European family population]'},{id:"B68",body:'[Kaati G, Bygren LO, Pembrey M, Sjostrom M. Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet. 2007;15(7):784-90]'},{id:"B69",body:'[Flannick J, Florez JC. Type 2 diabetes: genetic data sharing to advance complex disease research. Nat Rev Genet. 2016;17:535-549]'},{id:"B70",body:'[Hakim O, Misteli T. SnapShot: chromosome confirmation capture. Cell. 2012;148:1068.e1-1068.e2]'},{id:"B71",body:'[Nica AC, Dermitzakis ET. Expression quantitative trait loci: present and future. Philos Trans R Soc Lond B Biol Sci. 2013;368:20120362]'},{id:"B72",body:'[Chen Z, Yu H, Shi X, Warren CR, Lotta LA, Friesen M, Meissner TB, Langenberg C, Wabitsch M, Wareham N, Benson MD, Gerszten RE, Cowan CA. Functional screening of candidate causal genes for insulin resistance in human preadipocytes and adipocytes. Circ Res. 2020;126:330-6]'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Sanghoo Lee",address:"sprout30@scllab.co.kr",affiliation:'- Companion Biomarker Center, SCL Healthcare Co., Ltd., Gyeonggi-do, 16954, Republic of Korea
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Introduction
Assuming that care for the environment is more than just a matter of technical adaptations, it is worthwhile to delve into the religions. Will they serve as an incentive to necessary changes in our dealing with creation, or are they tributary to our problems? We limit ourselves to the so-called Abrahamic religions: Judaism, Christianity, and Islam. This not because only these religions have something to contribute, but because of their similar basis in the creation story they can be treated together (without, incidentally, suggesting that their message as to creation is identical). In the course of our discourse, we will have occasion to side glance at other religions as well, although each religion would deserve a separate treatment.
First, we will deal with the religious perspective on the human being and on humankind, to continue with more specific religious notions of care for the environment.
2. Religious perspectives on the human being
Undoubtedly, the notion of the human being created in God’s image as stated in Genesis 1:27 is a cornerstone of the Abrahamic religious perspective on human beings. Critical voices argue that here already the exploitation of the earth finds its legitimation: The human being is distinguished from the other living creatures, created “according to their species.” Hence, a closer look is necessary. Indeed, Genesis 1:26 allows the human being to rule over the other living creatures. A few verses further, God even instructs the human being “to fill the earth and to subdue it” (1:28). Small wonder that critical voices point to texts such as these to accuse the religions of complicity in exploiting the earth.
Let us take a closer look by drawing upon the interpretations the religions themselves offer. Indeed, humankind is presented as separated from the rest of the living animals. Although both human beings and animals are creatures and as such related to each other, God addresses only the human being directly, vouchsafing him the dignity of being created in God’s image. This dignity is explained ethically, rather than ontologically: The human being bears a responsibility for all of creation, and just like the First Human Being, the Adam Kadmon (both male and female) has been entrusted with the whole of creation. In that respect, each individual may consider him- or herself as equal to the First Human Being.1 Obviously, we cannot expect from animals to fulfill such a responsibility and although the human being has often forfeited this responsibility he should be considered capable of doing otherwise. The statement, often heard from activists of the environment, that the human being is “just and animal,” fails to acknowledge this special responsibility. Still, the statement finds its origin in a typically human concern for the whole of creation.
The anthropocentric reading of Genesis ignores the fact that the day of rest is intended for both human beings and animals. It likewise fails to assess the specifics of the covenant between God and Noah in which the animals are included as partners of the covenant (Genesis 9:10). Only then a certain alienation between human beings and animals seems to be emphasized (Genesis 9:2), as if Adam and Eve in paradise lived more harmoniously with their fellow creatures the animals than humankind outside paradise. This may have fostered the idea that initially Adam and Eve were not allowed to eat meat, happy as they were as vegetarians. Only after humankind had shown how much evil it could spread, the eating of meat would have been allowed (Genesis 9:3). Hence, the eating of meat may be interpreted as a concession to the cruelty of humankind and to prevent him from doing violence to his fellow human beings. Even then, restrictions on eating meat remain in force: Blood as the seat of life is forbidden. The notion of divine permission to be asked before slaughtering an animal finds its origin in these texts. Ironically, ritual slaughter in Judaism and in Islam is often the target of attempts to abolish this practice, although the respect for animal life is a hallmark of it: Even a prayer is said over each individual animal is said before the slaughter.
In this perspective, vegetarianism is not an obligation, but can still be seen as an anticipation of messianic times, in which paradisiac vegetarianism will be restored. A peaceful relationship between the animals and the human beings belongs to the characteristics of messianic times, as can be seen by the many lives of saints in which an animal plays a role. In addition, some monastic rules prescribe a vegetarian menu. However, as with many messianic elements, enforcing vegetarianism without humankind being ready for it leads to violence and mutual dissension.
The notion of the human being created in God’s image knows of a plethora of religious interpretations, some of them seemingly rather exclusive. The banishment from paradise has been interpreted as a Fall of humanity, by which the dignity of the image of God has been obscured, rightly so if we consider the murder and deterioration described in Genesis 4-9. However, Christianity may claim that only redemption by Christ restores the image of God in the human being. This would imply an inability to act responsibly in all other human beings. This is, however, not the general line in Christianity: free will, although damaged by the Fall, is never completely absent. Distinguishing between the image of God and the likeness of God (Genesis 1:27), some theologians argue that the image of God should be considered a permanent state, whereas the likeness invites to imitatio Dei, by obeying His commands. Anyway, the notion of dignity-as-responsibility does seem to be preserved here as well.2
Greek-orthodox theology has always emphasized the dignity of the human being more than his condemnation after the banishment from paradise. An interesting theology of the environment connects the human being again the First Human Being in paradise. Just like in Paradise, the good of the earth has been celebrated as God’s gift to humanity; nowadays, the Human Being should be considered a priest of creation, receiving the gifts of the earth in gratitude, consciously of the Giver of all these benefits and rendering grace for that. If humankind would be conscious of having received the goods of the earth, humankind would not consider himself as the sole possessor of the goods, but he would be willing to share with others what he has received himself.3 Possibly, some similarity with the cosmic notions of the human being within Hinduism may be detected here. Obviously, the creatio ex nihilo (creation from nothing) has fostered the independence of the human being, but at the possible expense of an absence of the divine in creation. In contrast, both Greek-orthodox theology and Hinduism reckon with an incarnatory theology of the divine presence in the world, the one by viewing the incarnation as a cosmic event, affecting the destiny of all living creatures, the other by affirming avatars as manifestations of the divine and by assuming a continuity between human beings and animals (reincarnation) and by considering some animals sacred. Add to this the fact that the Jewish mysticism, known as Kabbalah has transformed the creatio ex nihilo into its opposite by claiming that the Nothing (=God) has effused Himself into creation, and it will be clear that Kabbalah as well may be seen as an ally in environmental spirituality. The parallelism between macrocosm and microcosm known in Kabbalah and in many other religious manifestations, likewise bridged the gap between the divine and the world.
The Greek-orthodox concept of priestly dignity is undoubtedly also a correction of the ambiguous notion of the human being as the steward of creation. This notion has been derived from the parables in the New Testament, in which it denotes the human responsibility to develop and increase the wisdom/Torah received from God. In the course of history, this notion of stewardship of the talents has been taken literally, as money, instead of metaphorically, as God’s wisdom. It began to serve as a legitimation of capitalist increase of money and wealth. Coupled with the obligation that wealth should be re-invested rather than enjoyed,—“in the sweat of your face you will eat your bread”(Gen 3:19)—sociologists like Max Weber and Richard Tawney detected in this religious notion a possible foundation of capitalism. Be it as it may, the human being as priest of creation allows for an generous distribution of wealth and a sincere enjoyment of God’s good gifts, deserved to be treated with holy reverence.
It should be noted that Islam is hesitant to use the concept of human being as “image of God.” No doubt, fear of a too anthropomorphic speaking about God lies at the heart of this hesitance. Although it should be stressed that according to the Bible, God creates the human being in His image, which should not be confused with the human being creating God in his image, the Islam keeps aloof from this concept.4 The concept to denote the dignity of the human being in the Qur’an is: ḥalif, which can be translated as: vice-regent (Qur’an 2:30). Bold interpreters of the Qur’an claim that the human being is here considered God’s vice-regent on earth. Others point to the fact that in the context of the creation of the human being, the protest of the angels against the creation of the human being has been silenced.5 Hence, the human being could be considered as the successor of the angels (although his being a ḥalif is located on earth, not in heaven!). The context of the Qur’anic account is remarkably similar to the Genesis account in that the human being is considered capable of all kinds of cruelty and depravity. The angels are quick to emphasize that. Yet the dignity of the human being allows for more noble expectations from him as well.
2.1 Nature and history
From a more general perspective, it is clear that the Hebrew Bible knows of many regulations about animals. They should be treated with care and without vexing them, allowing them to rest together with the human beings. The long lists of pure and impure animals, which has laid the basis of kashrut, often lack a rational foundation, but retain the animal in the religious consciousness. In addition, Biblical feasts such as Pesach and Shavuot (Feast of Weeks) are based upon agriculture. Due to German protestant influence upon Biblical scholarship, this attachment to nature has been downplayed in favor of the dimension of history.6 Obviously, Pesach celebrates the liberation from slavery in Egypt, but the agricultural aspects should not be overlooked. The bone of the lamb as representation of spring and the of the new-born of the flock, the unleavened bread, and many other elements still betray the agricultural layer.7 Due to an ideological bias against nature as supposedly more prone to idolatry and to veneration of a goddess of the earth and of fertility, German exegetes like Von Rad staunchly combatted all references to nature in Biblical feasts. By doing so, they robbed the Bible of its ability to solidarize human beings religiously with their fellow creatures. Particularly, feminist scholars have criticized this ideological approach to nature in Biblical context.
In the course of history, animals have more or less disappeared from the religious consciousness, except for farmers who, in spite of an industrialized agriculture, still feel attached to their animals. Not long ago, the day of slaughtering animals was still celebrated as a feast of thanksgiving to God. Hence, we should not blame the Bible for ignoring animals and all of creation, but rather an anthropocentric reading of the Bible as it has developed in Western society, possibly only after the Middle Ages. Whereas in the Middle Ages, according to some thinkers the tripartite division of the soul in a vegetative animal and human soul, as proposed by Aristotle, were all of them present in the human being, Western philosophy has ignored the position of nonhuman creatures until recently.8
Another relevant topic when it comes to Bible and environment is time perception. The noncyclical linear time perception of monotheistic religions is held responsible for exploiting the earth.9 The linear time concept would have fostered a blind faith in progress and expansion. Suffice it to state that the notion of a last judgment can indeed be understood as the End of Time, but also as the ultimate expression of human responsibility for his behavior. This last element is, however, sadly neglected in Christianity. The cyclical time perception in Hinduism may have led to an undervaluation of history, but also to a less result-driven approach to life.10 Mutatis mutandis the African concept of time in which the remote future does not seem to play an essential role (John Mbiti) may provide a less-exploiting attitude to the environment. However, all this needs further scrutiny.
3. Some specific religious regulations about environmental protection
Pope Francis has surprised the world with his encyclical Laudato Si’ (2015).11 The document propagates an inclusive ecology combined with economic reform. It points to the problems of the poor countries which suffer the most under the ecological crisis. “The interconnectedness of all creatures (not only human beings) invites to acknowledge the worth and dignity in love and admiration”.
The encyclical develops this concept in five sections: ecology of the environment; cultural ecology; ecology of daily life; the principle of the common good; and: justice among the generations.
Ecology of the environment (1) should prevent the human being from considering nature as a mere object outside himself. Resorting to the notion of creation (instead of the more physical term nature) the interconnectedness of all creatures and creation as a gift of God are stressed. From the outset, the human being is implicated in the notion of “creation.” The notion of nature with its duality of culture is less clear in that respect. The encyclical rejects fatalistic approaches to the ecological crisis by stating that an overly anthropocentric approach to the world has caused a one-sided exploitation of the earth.
Surprisingly, concern for the destruction of local cultures (2) is also one of the topics about the ecological crisis. Destruction of large forests often go hand in hand with oppression of local cultures. These locals could be of service as keepers of the forests and of wildlife.
The ecology of daily life (3) should analyze the way people live together in towns and suburbs. The feeling of togetherness can be enhanced by a humane architecture in which people do not feel lost or superfluous.
The common good (4) presupposes the respect for the human person and the human rights.
Last but not the least, justice among the generations (5) introduces a new notion of responsibility, in which future generations are included as well as the respect for the heritage of past generations.
The encyclical ends with introducing the term: ecological conversion. Conversion to God and to creation is the only way to spiritually combat the ecological crisis we are in.
Turning to Judaism: The Jewish scholar and Rabbi Norman Solomon distinguishes six basic principles in the Jewish approach to the environment [7]:
The creation is good and God (who should be distinguished from creation) may be praised because of that;
Biodiversity should be guarded according to the Bible. Each animal is created according to its species;
The hierarchy of living creatures with the human being at the top should be acknowledged accompanied with this principle: the higher the ranking the higher the responsibility
Human beings are responsible for the active maintenance of all life.
Land and people belong together. This would imply for the Jewish people exemplary way of dealing with water, the soil, and the air in the land of Israel.
Do not waste. This Biblical injunction (Deuteronomy 20:19) can be applied to water and chemical waste12
Islam may be less known for its environmental thought. Still already in the Middle Ages, the animals are told to start a lawsuit against the human beings because of the bad treatment by the latter.13 The Islamic scholar Abdelilah Ljamai brings forward a plethora of literature about environmental care, hardly known in Europe and America [9]. Some of the Muslim writers he quotes are critical about the way Islamic countries deal with the environment. They resort to the Qur’an, to post-Quranic narratives, and to Islamic jurisprudence in order to develop an Islamic environmental ethics. The worldview of the Islam consists of three principles:
The cosmos reflects the glory of God;14
The cosmos may be taken into service of humankind;
Destruction of nature is a gross form of injustice.
Nonhuman beings have an intrinsic value and hence, the concept of rights of animals is not alien to Islam, as our example above has shown.
Striking are the practical exhortations, often backed up with some saying allegedly going back to Muhammad: plant trees; revive dead soil (one is even entitled to become the owner); prohibition to pollute the air; moderate eating; careful handling of water resources (prohibition to defecate); withdrawal of water for one’s own field should not happen at the expense of other farmers. Both in traditional Islamic sources and in modern publications emphasis upon the rights of animals and the rejection of cruel treatment of animals can be found [11].
4. Conclusion
The way we have dealt with religious perspectives on the environment is both hermeneutic and benevolent. Hermeneutic because it allows for a merging of ideas of the past with our modern horizon of understanding. This is in marked contrast to historic-critical approaches which aim at a reconstruction of past phenomena without taking into account our modern world.
Our approach is also benevolent: Obviously, people from centuries ago did not have the same sense of urgency and the same knowledge of technological issues as we have. The examples quoted above should be considered paradigmatic rather than identical to modern issues. They may offer spiritual vistas to be explored further, without claiming to offer exhaustive solutions or direct applications. Still, the spiritual depth of these religious traditions may surprise us, accustomed we are to assume the preeminence of our own technological era. The advancement on the spiritual level, if at all, is less clear than on the technological level. A future for our planet cannot dispense with spiritual resources such as these. A broad perspective on religions and spiritualities, critically assessing its possibilities and stumbling blocks, may contribute to overcoming the spiritual crisis of the human attitude to the environment.
\n',keywords:"animals and humans, hermeneutics of creation stories, Abrahamic religions, image of god, feminist criticism, anti-nature theology",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81075.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81075.xml",downloadPdfUrl:"/chapter/pdf-download/81075",previewPdfUrl:"/chapter/pdf-preview/81075",totalDownloads:12,totalViews:0,totalCrossrefCites:0,dateSubmitted:"January 20th 2022",dateReviewed:"February 24th 2022",datePrePublished:"April 2nd 2022",datePublished:null,dateFinished:"April 2nd 2022",readingETA:"0",abstract:"The relationship between Abrahamic religions and environment is a delicate one. Critical voices argue that already in Genesis the human being is situated in a hierarchical position above the animals. Only by admitting his animal status humankind could be freed from its arrogance. Other voices point instead to the solidarity between human beings and animals as fellow-creatures. Particularly in Jewish interpretation (midrash), the dignity of the human being goes together with responsibility for the whole of creation, a responsibility which cannot be required from animals. In addition, the seventh day is a day of rest for human beings and for animals. It is our anthropocentric reading of the Bible that has excluded animals from our religious consciousness. In this chapter, the religious attitude toward animals and to nature in the three Abrahamic religions will be documented. a bit more. A purely anthropocentric reading of sacred Scripture has been dominant the last centuries, but fails to do justice to the Bible. The protestant bias against nature by identifying it with idolatry and with fertility cults of a goddess has also caused a blind spot for the environment in religious perspective.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81075",risUrl:"/chapter/ris/81075",signatures:"Marcel Poorthuis",book:{id:"11429",type:"book",title:"Sustainability, Ecology, and Religions of the World",subtitle:null,fullTitle:"Sustainability, Ecology, and Religions of the World",slug:null,publishedDate:null,bookSignature:"Dr. Levente Hufnagel",coverURL:"https://cdn.intechopen.com/books/images_new/11429.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-436-5",printIsbn:"978-1-80355-435-8",pdfIsbn:"978-1-80355-437-2",isAvailableForWebshopOrdering:!0,editors:[{id:"10864",title:"Dr.",name:"Levente",middleName:null,surname:"Hufnagel",slug:"levente-hufnagel",fullName:"Levente Hufnagel"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Religious perspectives on the human being",level:"1"},{id:"sec_2_2",title:"2.1 Nature and history",level:"2"},{id:"sec_4",title:"3. Some specific religious regulations about environmental protection",level:"1"},{id:"sec_5",title:"4. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'[Solomon N. The image of god in man from a Jewish perspective. In: Solomon N, Harries R, Winter T, editors. Abraham’s Children. Jews, Christians and Muslims in Conversation. London: T&T Clark; 2006a. pp. 147-153]'},{id:"B2",body:'[Michot Y. The image of god in humanity from an Islamic perspective. In: Solomon N, Harries R, Winter T, editors. Abraham’s Children. Jews, Christians and Muslims in Conversation. London: T&T Clark; 2006. pp. 163-174]'},{id:"B3",body:'[Van MT. Green Theology. An Eco-Feminist and Ecological Perspective. London: Darton, Longman and Todd; 2022]'},{id:"B4",body:'[White L. The historical roots of our ecological crisis. Science. 1967;55:1203-1207]'},{id:"B5",body:'[Poorthuis M. Rituals in Interreligious Dialogue: Bridge or Barrier? Newcastle: Cambridge Scholars Publishing; 2020]'},{id:"B6",body:'[Verkleij Frans. “Bekering tot integrale ecologie. De boodschap van paus Franciscus in zijn encycliek Laudato Si”. In: Bas van den Berg and Leo Mock (eds), Zorg voor de aarde, herstel van de wereld. Amsterdam: Pardes / Amphora; 2021. pp. 108-144]'},{id:"B7",body:'[Solomon N. The environment from a Jewish perspective. In: Solomon N, Harries R, Winter T, editors. Abraham’s Children. Jews, Christians and Muslims in Conversation. London: T&T Clark; 2006b. pp. 248-256]'},{id:"B8",body:'[Brethren P. The Animal’s Lawsuit against Humanity. Fons Vitae Publishers / Oxford: Oxford University Press; 2010]'},{id:"B9",body:'[Ljamai Abdelilah. “Ecologisch bewustzijn in de islam. De islamitische milieu-ethiek heroverwogen”. In: Bas van den Berg and Leo Mock (eds). Zorg voor de aarde, herstel van de wereld. Amsterdam: Pardes/Amphora; 2021. pp. 146-185]'},{id:"B10",body:'[Radwan L. The environment from a Muslim perspective. In: Solomon N, Harries R, Winter T, editors. Abraham’s Children. Jews, Christians and Muslims in Conversation. London: T&T Clark; 2006. pp. 272-283]'},{id:"B11",body:'[Foltz R. Animals in Islamic Traditions and Muslim Culture. This book deals with the cosmic, juridical and literary status of animals in Islam. New York: One World; 2014]'}],footnotes:[{id:"fn1",explanation:"See [1]."},{id:"fn2",explanation:"The most serious threat to this universal dignity is the reasoning that only the male human being would be created in God’s image, whereas the female would be created according to the example of the male (cp. 1 Cor 11:7). I consider this gendering as a sidetrack, caused by a practical inability to accord to women the same dignity and responsibility in church as to men."},{id:"fn3",explanation:'The "green Patriarch" Bartholomew of Constantinople has developed this priestly concept into an environmental theology.'},{id:"fn4",explanation:"See for a nuanced treatment which allows for exceptions: [2]."},{id:"fn5",explanation:"It should be noted that the protest of the angels against the creation of the human being can be found in the Jewish interpretations of Genesis (Midrash Rabba) as well."},{id:"fn6",explanation:"See: [3]."},{id:"fn7",explanation:"Note how the search for unleavened bread in the houses betrays a sedentary civilization (Exodus 12:15), although the Israelites are on the eve of 40 years of desert!"},{id:"fn8",explanation:'If a dualism between body and mind may have fostered such an anthropocentric reading, the philosopher Descartes may have been the culprit, as he laid the foundation for a "ghost in the machine" concept of the human being.'},{id:"fn9",explanation:"One of the first to bring forward this accusation is [4]."},{id:"fn10",explanation:"The shared interest for the animal sacrifice as the basic religious attitude has surprisingly fostered affinities between Hinduism and Judaism. The same holds good for the bodily orientation towards purity rules. See my book: [5]."},{id:"fn11",explanation:"See the overview in: [6]."},{id:"fn12",explanation:"However, the obligation to keep the camp in the desert clean (Deuteronomy 23:13), brought forward by Solomon, op. cit. 252, as an example of environmental care, does not seem to be very appropriate, as the garbage is allowed to be thrown outside the camp! This is quite similar to the European habit to dump chemical waste in Arica."},{id:"fn13",explanation:"See the Sufi text, probably from the 10th century: [8]."},{id:"fn14",explanation:"Lufti Radwan [10] emphasizes the connection between the unity of God (tawḥid) and the unity of the created world, which is especially relevant given the objections against monotheism as intolerant and anti-nature."}],contributors:[{corresp:"yes",contributorFullName:"Marcel Poorthuis",address:"m.j.h.m.poorthuis@tilburguniversity.edu",affiliation:'- Tilburg University, Utrecht, The Netherlands
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He was born in Tokyo on April 1971 and received his doctor degree of engineering in light-wave sensing technology from Tokyo Institute of Technology in 1999. After that he arrived at Saitama University as an assistant professor. He was previously in the national research institute (CNR) in Italy as a guest researcher from October 2005 to March 2006. He has been the current position since 2006.\nDr. Hijikata has been interest in characterizations of surfaces and interfaces of SiC semiconductor material for its device applications, especially on characterizations and processing of MOS interfaces as well as on the oxidation mechanism of SiC.",institutionString:null,institution:{name:"Saitama University",institutionURL:null,country:{name:"Japan"}}},{id:"18271",title:"Prof.",name:"Hiroyuki",surname:"Yaguchi",slug:"hiroyuki-yaguchi",fullName:"Hiroyuki Yaguchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"18272",title:"Dr.",name:"Sadafumi",surname:"Yoshida",slug:"sadafumi-yoshida",fullName:"Sadafumi Yoshida",position:"Invited researcher",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"18610",title:"Dr.",name:"Andrei",surname:"Los",slug:"andrei-los",fullName:"Andrei Los",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"19853",title:"Prof.",name:"Liudmila",surname:"Nickelson",slug:"liudmila-nickelson",fullName:"Liudmila Nickelson",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"Mob. Ph.: +3706 7103291\n\n 1987 - 2010 Physics Institute, Gostauto 11, LT-01108 Vilnius, Lithuania, Senior Researcher Scientist of Terahertz Electronics Laboratory, Electrodynamical Group Leader, Led and participated in the implementation of more than 10 contracts for microwave device development.\n\n2006 - Present Professor at Vilnius Gediminas Technical University (VGTU), Naugarduko 41, LT-032371 Vilnius, Lithuania\n\n2004 - 2006 Associate Professor at VGTU, Naugarduko 41, LT-032371 Vilnius, Lithuania\n\n2000 - 2001 Visiting Professor in Theoretical Physics, Department of Physics and Measurement Technology, Linköping University, S-581 83 Linkoping, Sweden.\n\n1991 - Postdoctoral research associate, Bristol University, UK, Department of Electrical and Electronic Engineering, Topic of Postdoctoral Investigation: “Analysis of Microstrip Lines on Anisotropic Substratesâ€.\n\n1973 - 1987 Junior Researcher, Semiconductor Physics Institute of Lithuanian Academy of Sciences, Gostauto 11, LT-01108 Vilnius, Lithuania.\n\n1966 - 1968 Electrical Design Engineer. Vilnius Electrical Factory “ELFAâ€, Vytenio 50, LT-03229, Vilnius, Lithuania.\n\n1966 - 1964 Engineer. Lithuanian State Committee on Standards, Laboratory of Control of Measuring Techniques, Odminu 4, LT-01122 Vilnius, Lithuania.",institutionString:null,institution:null},{id:"21616",title:"Prof.",name:"Victor",surname:"Los",slug:"victor-los",fullName:"Victor Los",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"editorial-policies",title:"Editorial Policies",intro:'All publications on this website are published under the Open Access model, without any subscription, registration, or access fees required from the user or his/her institution. In accordance with the Budapest Open Access Initiative's (BOAI) definition of Open Access, users are allowed to read, download, copy, distribute, print, search, and link to the full text versions of all Chapters. 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\n\nAll published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"7",type:"subseries",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. 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