1. Introduction
Stroke is the leading cause of neurological disability and among the leading causes of death worldwide. It is a focal neurological deficit that results from events that decrease or stop cerebral blood flow. As the consequence neurons cease functioning and irreversible neuronal ischemia and injury occur.
Broadly, strokes are classified into two main types-ischemic and hemorrhagic. Ischemic stroke (IS) is characterized by blockage in blood flow to a focal area of the brain, until hemorrhagic stroke is caused by bleeding into the brain. Acute IS is more common than hemorrhagic stroke. Although according the previous literature data about 80% of strokes wereischemic, the retrospective review from a stroke center found that about 60% were ischemic 1. Except their causes and pathophysiology ischemic and hemorrhagic types differ in their treatments and outcomes 2.
Based on the system of categorizing stroke developed in multicenter Trial of Org 10172 in Acute Stroke Treatment (TOAST), IS may be divided into the following major subtypes: large artery infarction, small-vessel (lacunar) infarction, and cardioembolic infarction. This classification on the basis of inferred origin of cerebrovascular occlusion 3 is the most frequently used. Other studies used systems based on clinical presentation or location and size of the lesion within the brain (such as the Oxfordshire Community Stroke Project system) 4. It classifies patients in five infarct types: cerebral infarction, lacunar infarct, total anterior circulation infarct, partial anterior circulation infarct, and posterior circulation infarcts. Many other classifications have been proposed, such as those from the Lausanne Stroke Registry and the Étude du profil Génétique de l’Infarctus Cérébral (GÉNIC) study 5,6. The first one included atherosclerosis with stenosis, atherosclerosis without stenosis, emboligenic heart disease, hypertensive arteriopathy, cerebrall hemorrhage, mixed causes and undetermined causes. The former included atherothrombotic stroke, cardioembolic stroke, lacunar stroke, arterial dissection, unknown causes stroke. Although stroke is often considered a disease of elderly persons, one third of strokes occur in persons younger than 65 years.
Risk factors for IS includes modifiable and non-modifiable etiologies. Non-modifiable risk factors include: age, sex, race, ethnicity, heredity, etc. Modifiable risk factors include the followings:hypertension, diabetes mellitus, hypercholesterolemia, atrial fibrillation, lifestyle factors, etc.Unfortunately, modifiable risk factors accounts for only approximately 60% of the population-attributable risk for stroke 7.
2. Genetic risk factors in stroke
Evidence continues to accumulate to suggest important roles for genetic factors in stroke. Genetic risk factors are particularly interesting, because they can offer a direct clue to the biological pathways involved. Genetic factors might affect stroke risk at various levels. They could act through conventional risk factors, interact with conventional and environmental risk factors, or contribute directly to an established stroke mechanism. They could further affect the latency of stroke or infarct size, and stroke outcome [8]. Stroke may be the outcome of a number of monogenic disorders or, more commonly, a polygenic multifactorial disease.
Evidence shows that genetic factors are more important in small- and large-vessel stroke than in cardioembolic stroke [9,10]. Some intermediate phenotypes also exhibit high heritability, such as carotid intima-medial wall thickness and white-matter lesions [8].
Genetic predisposition to stroke has been proven in animal models and in humans (twins, affected sibling pair, families). Several studies demonstrated higher rates of stroke among relatives of patients who died from stroke than among relatives of healthy control subjects. In a large study of stroke patients and age and sex matched controls, the odds ratios (ORs) of having a family history of stroke were 2.24 for large vessel-disease and 1.93 for small vessel disease [9]. Twin studies have confirmed a significant genetic component to stroke, with the stroke prevalence fivefold higher in monozygotic than in dizygotic twins [11]. Touze and Rothwell [12] in a metaanalysis based on 18 studies confirmed sex differences in heritability of IS; women with stroke were more likely than men to have a parental history of stroke, which is accounted for by an excess maternal history of stroke. Also, genetic predisposition could differ depending on age and IS subtype.
The initial expectancy to find only one or a few common mutations that substantially contribute to the risk of IS shifted toward the hypothesis of a large number of small-effect genetic variants with complex gene-gene and gene-environment interactions. The first approach used in identification of genetic variants contributing to stroke was linkage studies. Linkage analysis relies on the cosegregation of known polymorphic DNA marker with nearby, unknown disease-causing alleles in families. This approach was successful in monogenic diseases, but was less successful in the identification of genetic loci that contribute to the occurrence of polygenic stroke. The second approach was candidate gene approach.
2.1. Candidate-gene association studies of ischemic stroke
Until recently, candidate gene approach was the most common in genetic investigation of IS. A gene identified as a “candidate” is hypothesized to be involved in IS risk, and then, genetic variants, usually single nucleotide polymorphisms (SNPs), are identified within that gene. The SNPs are selected on the basis of their localization in genes which encode proteins with a known function in a biological pathway implicated in the pathophysiology of the disease. Then, the frequency of the SNPs is determined in a series of cases and controls and the obtained results are compared. They use a case-control study design. A gene variant that is more common in patients than in controls may cause stroke or be located close to the true causal variant.
Genes encoding products involved in lipid metabolism, thrombosis, and inflammation are believed to be potential genetic factors for IS [13-15. Although a large group of candidate genes have been studied, most of the epidemiological results are conflicting. Especially great interest is shown in exploring potential links between polymorphisms in genes encoding proteins involved in lipid metabolism and the risk of IS.
This chapter summarize the results of meta-analyses and case-control studies assessing the linkage of specific candidate genes with the risk of IS and specific subtypes. Electronic databases (Medline (http://www.ncbi.nlm.nih. gov/pubmed/), Embase (http://www. embase.com/), Google Scholar (http://scholar.google.com/), Yahoo (http://www.yahoo.com/), Kobson (http://www.kobson. nb.rs/) were searched until March 2012 and the obtained results were included in the text.
It is very well known that individuals with higher levels of plasma cholesterol, decreased high-density lipoprotein (HDL) and increased low-density lipoprotein (LDL) have a higher risk of premature atherosclerosis. The phenotype may arise not only from single gene disorders, but also from a number of genetic and environmental factors, including polymorphic variants of genes encoding the apolipoproteins, lipoprotein receptors and the key enzymes of plasma lipoprotein metabolism.
Seven metaanalyses [17-19,21-24] gave a positive association between the ε4 allele and IS. The first one [22], published in 1999, revealed a significantly higher apo4 allele frequency in affected patients compared with controls (OR 1.68, 95% CI 1.36–2.09, P0.001). In the next decade, five metaanalyses [17-19, 21,23] confirmed that ε4 allele carriers have a higher risk of IS compared with pooled ε2 and ε3 allele carriers in European populations, persons of non-European descent, Asians, Han Chinese and persons with early-onset IS. Performing large-scale meta-analysis (10674 cases/33430 controls) consisted of four meta-analysis [19,21-23] and 9 case-control studies [33,35,36,54,59,65,66,84,88], Hamzi et al. [24] calculated OR for the apo4 allele to be 0.95 (95%CI 0.77-1.14, P=0.002).
Approximately half of all casecontrol studies [26,27,29,33,38,41,45,47,49,51,53,54,57,58, 60,64,67,69,71,73-76,78-80,82,84,85,89-91,93-96,99,100] showed an increased frequency of the ε4 allele in stroke patients, making it a highly probable risk factor for IS; in four, significant association with large-vessel IS was observed. Three groups described the 2 allele as a risk factor for IS [76,85,94]. The status of the E2/3 genotype as a protective or risk factor is controversial. One report [100] demonstrated a protective role of the ε4 allele for small-vessel disease, and another [93] concluded that the E3/4 genotype could be a risk factor for lacunar stroke compared with the E3/3 genotype.
Several SNPs have been described in the 5’ regulatory region (c.491A>T, c.427T>C, c.219G>T, and c.113G>C), but current information is very preliminary. A higher risk of IS was associated with the G allele of the tightly linked c.219G>T and c113G>C promoter polymorphisms [96], and with the T allele of c.427T>C polymorphism [94]. One paper [94] reported the C allele of c.427T>C polymorphism as protective for IS.
Some authors have studied the association between IS and DNA polymorphisms in apoAI gene (
The apoB gene is located on chromosome 2q23, spanning approximately 43 kb and has 29 exons and 28 introns. ApoB polymorphisms (T71I (c>t; rs17246849), A591V (c>t; rs17240681),
The most promising results in IS studies are connected with apoA5 and apo(a) gene polymorphisms. It is well konown that apoAV is a member of apoAI/CIII/AIV gene cluster. apoAV gene consists of 4 exons and codes 369 amino acids protein. The common variants within the apoAV gene are associated with plasma tryglicerides (TG) levels, by enhancing the intravascular triglyceride hydrolysis by activating lipoprotein lipase (LPL), or can decrease the serum concentration of triglycerides through the inhibition of the hepatic very low density lipoprotein (VLDL) production. Literature data suggest significant association between apoAV gene polymorphisms (c.1131T>C, c.12238T>C, c.553G>T) and IS risk [34,109-112]. The association of apoAV 56G allele was observed in the large-vessel associated stroke group compared to the healthy controls [113]. The same group of authors [114] examined three polymorphism in apoAV gene in small-vessel, large-vessel and mixed subgroups of 378 patients with stroke and healthy controls. They found that patients carriers of -1131C and IVS3+476A alleles confer risk for all IS types, In this study the T1259C variant was not associated with IS that is in agreement with previous study of Jeromi et al.[112]. Recently published study on Han Chinese population confirmed the previously found association between c.1131T>C polymorphism in apoAV gene and IS risk [115].
There is growing and convincing evidence that elevated lipoprotein (a) levels have a significant role in stroke. Genetic studies demonstrated that Lp(a) is an inherited trait determined almost entirely by the apo(a) gene locus. Variations at the apo(a) gene locus beyond the kringle IV-2 domain seem to influence Lp(a) concentrations [116]. The pentanucleotide TTTTA repeat (PNTR) polymorphism located at the 5’ untranslated region of the apo(a) gene accounts for 10% to 14% of the variation in plasma Lp(a) concentrations [117], and was reported to be inversely correlated with Lp(a) levels. Low numbers of apo(a) TTTTA VNTR were associated with IS in three studies [118-120] that were included with the only meta-analysis [19] that evaluated the association of apo(a) TTTTA VNTR polymorphism and IS.
The Precocious Coronary Artery Disease (PROCARDIS) study identified 2 single-nucleotide polymorphisms (SNPs) at the Lp(a) locus (LPA) on chromosome 6q26–27 (rs3798220 (T/C) and rs10455872(A/G)) that each was strongly and independently related to Lp(a) levels and risk of coronary disease [121]. Wang et al. 122 in meta-analysisof 3550 IScases and 6560 controls showed no significant association of LPA variants previously associated with Lp(a) levels with IS (OR per allele 0.96, 95% CI 0.88-1.04, for rs1853021 and 0.95, 95% CI 0.88-1.03, for rs1800769). Also, there was the lack of evidence of an association of LPA score and prevalent or incident stroke in Heart Protection Study (1326 prevalent and 507 incident IS cases) [123]. It does not exclude the possibility that lowering Lp(a) could have beneficial effects on the risk of stroke or stroke subtypes. On the contrary, theWomen’s Health Study (123 IS cases) suggested a positive association of rs3798220 with stroke [124].
Future studies are warranted to assess whether the analysis of previously mentioned polymorphisms may be useful for the clinical approach to evaluate risk factors for IS.
The relationship between CETP polymorphisms and the risk of IS has been the subject of eight reports [28,30,34,131-135]. An association with CETP
The first published study in IS on 244 Hungarian patients [138] suggests a protective role for the
The human LPL gene is localized to chromosome 8p22, spanning 35kb. It contains 10 exons. The gene locus is highly polymorphic and contains many single nucleotide polymorphisms (SNPs) in both coding and non-coding regions. Some cause loss of enzymatic activity and others have only mild detrimental effects on LPL function, or serve more as markers for genetic variation elsewhere in the genome [148].
Epidemiological evidence on the potential role of LPL in IS remains scarce and controversial. Two SNPs in the coding DNA (cSNPs) that have been studied extensively cause point mutations in exons 2 and 6, with substitution of an aspartic acid to an asparagine residue at position 9 (D9N, p.Asp9Asn), and an asparagine to a serine residue at position 291 (N291S, p.Asn291Ser), respectively. These mutations occur at high frequencies in the general population (up to 5%) and are associated with elevated TG, decreased HDL-cholesterol levels, and concomitantly with a higher incidence of cardiovascular disease compared with non-carriers [149]. Polymorphism Ser447Ter is a consequence of a C to G transversion at nucleotide 1595 in exon 9, which converts the serine 447 codon (TCA) to a premature termination codon (TGA). This polymorphism is associated with increased lipolytic function and beneficial effects on lipid homeostasis and atheroprotection [148].
Four metaanalysis [16,153,154], and 17 casecontrol studies have been reported [28,30,34,72,88,94,132,152,155-163] about the association of LPL gene polymorphisms and IS. In a metaanalysis of six studies [153] the inverse association between LPL Ser447Ter polymorphism and IS risk was of borderline significance (OR=0.88, 95%CI 0.790.99, P=0.033). In recently published meta-analysis [154] of 4681 IS patients and 8516 controls from 13 studies LPL Ter447 variant was associated with a significantly reduced risk for IS (OR 0.79, 95%CI 0.68-0.93, P=0.005) in Causcasian and East-Asian population. According the data of four studies (387 cases/589 controls), this association was of great importance in atherosclerotic stroke (OR 0.44, 95%CI 0.32-0.62, P<0.00001). In the meta-analysis of same authors [154] that included 7 studies (3669 cases and 6693 controls) no significant association between Ser291 variant and IS stroke risk was found. This is in accordance with the conclusion of previously published meta-analysis of LPL Asn291Ser polymorphism and IS [16]. A positive association between S447X variant and stroke has been reported in specific subtypes, as in the study of Shimo-Nakanishi et al. [152], Zhao et al. [160], Guan et al. [161], and Xu et al. [163] which reported a relationship with atherosclerotic stroke, and in the prospective cohort study of Morrison et al. [72] who described a positive association between S447X and asymptomatic stroke lesions, and in the study of Kostulas et al. [162] where the protective role of G-allele of LPL S447X polymorphism had a lower frequency in males. Shimo-Nakanishi et al. [152] observed a protective role of H- H- and H-H+ genotypes vs. H+H+ (
Two non-synonymous
According the literature data there are three metaanalysis [18,174,175] and 26 casecontrol studies [28,30,34,35,176-197] explored the association of PON1 polymorphisms and IS risk. A positive association of Gln192Arg PON1 polymorphism and IS was described in the metaanalyses and in five case-control studies [177,178,184,185,188], but this association was negative in all other reports. Only two studies in Turkish populations obtained evidence for a positive association of Leu55Met PON1 polymorphism and IS [188,193], in contrast to 12 where no evidence for this association was found [28,30,177-179,181,186,187,190-192,194].
Two recently published meta-analysis included the studies examined the association of two common polymorphisms in the coding region of PON1 gene (rs662 and rs854560) and the occurrence of IS. In meta-analysis [174] of 22 studies (7384 cases/11074 controls) PON1 polymorphism rs662 was associated with increased risk for IS (OR 1.10 per G allele copy, 95%CI1.04–1.17, P=0.001), while no significant association of rs854560 was observed in meta-analysis of 16 eligible studies (OR 0.97 per T allele copy, 95% CI 0.90–1.04, P=0.37). The other meta-analysis [175] included 8 studies on rs854560 polymorphism and 9 studies on rs662 polymorphism. This analysis provides strong evidence that the rs662 polymorphism of PON1 gene is associated with IS (OR 1.21, 95%CI 1.02-1.43, P=0.03), and that the rs854560 gene polymorphism is not associated with IS (OR 1.12, 95%CI 0.96-1.31, P=0.13).
Man et al. [198]in 191 Han Chinese patients with acute IS, of whom 25% had concurrent stenosis found that genotype distributions of PON1 Q192R differed significantly between patients with stroke and controls, and that the presence of at least one R allele in PON1 Q192R was associated with concurrent stenosis.
Polymorphism c.107C>T is important because it contributes 23% of the variances in PON1 levels. Since the presence of T at position -107 of the PON1 gene disturbs a recognition sequence for stimulating protein-1 (Sp1), the TT genotype is associated with the lowest serum PON1 levels. Although the frequency of the T allele and TT genotype did not differ significantly between young adults with arterial IS and controls, the presence of the -107T allele was associated with an independent increase in the risk of arterial IS [197].
There are two common polymorphisms of the PON2 gene: A148G (Ala148Gly) and C311S (Ser311Cys)). Almost all research groups except one [192] agree that there is no significant association between IS and these polymorphisms [28,30,177,181,187,199] Four polymorphisms in the PON3 gene were examined in two studies on IS patients [181,187]. No evidence for an association was obtained. Whereas rs662 (c.575A>G or p.Gln192Arg) polymorphism of the PON1 gene could be regarded as a potential risk factor for IS, this does not seem to be the case for PON2 and PON3.
Although, Lazaros et al. [200] did not identified none of the PON polymorphisms (PON1(Q/R) 192, PON1(M/L) 55, and PON2(S/C) 311) as a risk factors for IS, they concluded that PON2 311C allele was significantly increased in patients with severe forms of IS and could be reviewed as a possible predisposing factor for severe cases of IS.
Large-scale multicenter-controlled prospective studies are warranted to further explore the effects of PON polymorphisms on stroke susceptibility and severity.
Only few studies explored the association of LDLR gene polymorphisms and IS. Guo et al. [201] investigated the relationship between
Oxidized LDL that play a key role in the atherogenesis process exert most effects through the interaction with its major receptor lectin like oxidized low density lipoprotein receptor 1(LOX-1). LOX-1 is encoded by the lectin like oxidized low density lipoprotein receptor 1 (OLR1) gene, located in the p12.3–p13.2 region of human chromosome 12 and consists of 6 exons. Few SNPs located within introns 4, 5, and 3′ untranslated region, are associated with higher risk of developing acute myocardial infarction. Polymorphism (rs11053646, G501C) located in exon 4, leads to a change from a lysine to an asparagine at position 167 (K167N). As the consequence, reduced binding and internalization of the oxLDL was noticed. Only one paper [205] relates G501C polymorphisms of the OLR1 gene and IS, with negative results. Except LOX-1 full receptor, LOXIN as an isoform lacking part of the functional domen was identified and it has a protective role by blocking LOX-1 activation. One recently published study examined the prevalence of OLR1 gene polymorphisms, IVS4-14 A/G and IVS4-73 C/T, which regulate the expression of LOXIN, in 43 patients with ischemic cerebrovascular diseases (ICVD). Patients with G homozygosity for IVS4-14 polymorphism and T homozygosity for IVS4-73 polymorphism have higher risk to develop ICVD [206].Man et al. [198]in 191 Han Chinese patients with acute IS, of whom 25% had concurrent stenosis examined whether oxidized low-density lipoprotein receptor (OLR) 3 untranslated region (UTR) C > T (rs1050283) polymorphism and found that TT allele in OLR rs1050283 were associated with concurrent stenoses.
The association of LDLR and OLR1gene polymorphisms with IS should be further assessed in different populations and in wider series of patients.
Genetic studies links polymorphisms in the human EPHX2 gene with modified risk of IS in a number of human populations [216-218]. In the Fornage’s study, a positive association was observed between the Glu470Gly variant and the incidence of IS in African American cohort [216].
Zhang et al. [218] examined potential associations between
Fava’s study [221] examined whether the EPHX2 missense K55R and R287Q, together with the –1452T>C (rs7003694) in the promoter region and the +1784A>G (rs1042032) in the 3UTR polymorphisms, are associated with hypertension and with risk of cardiovascular events in middle-aged Swedes.They found no significant difference in the incidence of IS in carriers of different EPHX2 R287Q, EPHX2 –1452T>C genotypes, EPHX2 +1784A>G (P>0.05), until the higher incidence of IS was evident in male EPHX2 R-homozygotes versus male K-allele carriers.
2.2. Genome-wide association studies (GWAS) in ischemic stroke
The completion of the Human genome project, together with rapid improvements in laboratory techniques in this field, has enabled investigators to examine multiple genetic variants simultaneously in large study populations and it can be used for unlocking the genetic basis of complex human diseases [222,223]. The genetic variants that can be identified by GWAS are common SNP and have low effect size. By introducing GWAS a major limitation of the candidate gene study was overcame and candidate gene studies have now been largely superseded by the GWAS technique.
To date, GWAS of IS has been performed in 6 cohorts, resulting in 7 publications with somewhat inconsistent results. The initial step in a genome-wide genotyping study in patients with IS was performed in 2007 [224]. The analysis which compared 408,803 unique SNPs in 249 white patients with IS and 268 white neurologically normal controls in five US stroke centers do not suggest any single common genetic variant exerting a major risk for IS. The other recently published genome-wide association study [225] found a significant association between two SNPs rs11833579 and rs12425791on chromosome 12p13 with total, ischemic, and atherothrombotic stroke in white persons. The SNPs are located closed to the gene Ninjurin2 (nerve injury-induced protein 2-NINJ2) and WNK1-serine-threonine kinase that regulate ion channels involved in sodium and potassium transport. Finally, SNPs in paired-like homeodomain transcription factor 2 (
Three GWAS were performed in Japanese populations. Kubo et al. [228]found significant association of non-synonymous SNP (1425 G⁄A) in protein kinase C-eta (PRKCH) with lacunar infarction in the pathogenesis of IS. Hata et al. [229]found that SNP in the 5'-flanking region of angiotensin receptor like-1 (AGTRL1) gene (rs9943582, - 154G/A) to have a significant association with brain infarction. Also, rs9615362 of cell surface receptor CELSR1 (cadherin epidermal growth factor laminin A seven-pass G-type receptor 1) was associated with IS [230].
3. Conclusion
Genetics of IS represents a unique challenge. Among the most examined candidate genes in IS are those associated with lipid metabolism. Unfortunately, the results are complex and far from clear-cut. According the literature review in this chapter it can be consluded that genes (polymorphisms) that are the most likely to be associated with IS are: apoE (apo ε2/ε3/ε4) and PON1gene (p.Gln192Arg). Insufficient or inconsistent data that neither supported nor excluded an association of some genes polymorphisms with ISapoAV (c.1131T>C), LPA (rs3798220), LPL (S447X), LDLR (c.370A>T), OLR1(IIVS4-14A/G, IVS4-73C/T) and EPHX2 (G860A). For other genes/polymorphisms that were reviewed in this paper, we are reasonably confident that an association with IS can be ruled out.
The reasons for contradictory results in the studies may be limited sample size, heterogeneity of study designs and endpoints, differences in inclusion and exclusion criteria, ethnically different patient populations, selection of control population, different stroke subtypes and age of stroke onset, type of statistical evaluation, covariates, correction for multiple testing etc.One of the limitations of multiple non-reproducible candidate gene studies was the restriction to a single or rather few genetic variants tested for association with disease in examined gene. Further, genetic variants of candidate genes with strong effects at the transcriptional level or others affecting the functionality of the protein may have escaped the test for association with disease risk. Thus, in retrospect, it is not surprising that the candidate gene approach resulted in only limited success in the elucidation of IS stroke genes.
Research in the field of IS should be directed towards facilitation of the characterization of IS pathogenesis at the molecular level and the development of genetic markers’ panels for assessment of IS risk. Technological developments such as GWAS, NGS technology, transcription profiling and proteomics will provide huge amounts of genetic information and allow investigators to identify variants in patients with specific stroke subtype and to identify how they exert their effects at the molecular level. The replication in an independent study, in large and well-characterized groups of patients of different ethnic origin, is required to confirm previously obtained results.On the basis of genetic or genomic information the therapeutic outcome or side effects in stroke patients could be predicted, as the effectiveness and safety of applied therapy. Also, this approach may help in stroke prevention by identification of presymptomatic at-risk individuals, resulting in minimizing patients’ morbidity and mortality and reducing health care costs associated with stroke.
References
- 1.
Am J Emerg MedShiber J. R. Fontane E. Adewale A. A. Stroke registry. vs hemorrhagic ischemic. strokes 2010 28 3 331 333 - 2.
Baird AE. Genetics and genomics of stroke. J Am Coll Cardiol2010 56 4 245 253 - 3.
Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. StrokeAdams H. P. Bendixen B. H. Kappelle L. J. Biller J. Love B. B. Gordon D. L. EE Marsh 1993 24 1 35 41 - 4.
LancetBamford J. Sandercock P. A. MS Dennis Burn. J. CP Warlow Classification. natural historyof. clinically identifiable. subtypes ofbrain. infarction 1991 337 8756 1521 1526 - 5. Bogousslavsky J, Van Melle G, Regli F: TheLausanne Stroke Registry: analysis of 1,000consecutive patients with first stroke. Stroke1988;19(9):1083-1092.
- 6. Touboul PJ, Elbaz A, Koller C, Lucas C, AdraiV, Chedru F, Amarenco P, GENIC Investigators:Common carotid artery intima-mediathickness and ischemic stroke subtypes: theGENIC case-control study. Circulation2000;102(3):313-318.
- 7.
Whisnant JP. Modeling of risk factors for ischemic stroke. The Willis Lecture. Stroke1997 28 9 1840 1844 - 8.
Genetics of ischaemic stroke. Lancet NeurolDichgans M. 2007 6 2 149 161 - 9.
Heritability of ischemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies. StrokeSchulz U. G. Flossmann E. Rothwell P. M. 2004 35 4 819 824 - 10.
Evaluating the genetic component of ischemic stroke subtypes: a family history study. StrokeJerrard-Dunne P. Cloud G. Hassan A. Markus H. S. 2003 34 6 1364 1369 - 11. Brass LM, Isaacsohn JL, Merikangas AR. A study of twins and stroke.Stroke 1992;23(2):221-223.
- 12.
Sex differences in heritability of ischemic stroke: a systematic review and meta-analysis. StrokeTouzé E. Rothwell P. M. 2008 39 1 16 23 - 13.
Genetics and ischaemic stroke. BrainHassan A. Markus H. S. 2000 Pt 9):1784-1812. - 14.
Genetic polymorphisms for the study of multifactorial stroke.Hum MutatBersano A. Ballabio E. Bresolin N. Candelise L. 2008 29 6 776 795 - 15.
Genetic aspects of ischemic stroke: coagulation, homocysteine, and lipoprotein metabolism as potential risk factors. Crit Rev Clin Lab SciStankovic S. Majkic-Singh N. 2010 47 2 72 123 - 16.
Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch NeurolCasas J. P. Hingorani A. D. Bautista L. E. Sharma P. 2004 61 1652 1662 - 17.
Xin XY, Song YY, Ma JF, Fan CN, Ding JQ, Yang GY, Chen SD. Gene polymorphisms and risk of adult early-onset ischemic stroke: A meta-analysis. Thromb Res2009 124 5 619 624 - 18.
Meta-analysis of genetic studies from journals published in China of ischemic stroke in the Han Chinese population. Cerebrovasc DisXu X. Li J. Sheng W. Liu L. 2008 26 1 48 62 - 19.
Genetics of ischaemic stroke among persons of non-European descent: a meta-analysis of eight genes involving approximately 32,500 Individuals. PLoS MedAriyaratnam R. Casas J. P. Whittaker J. Smeeth L. Hingorani A. D. Sharma P. 2007 e131. - 20.
Ischaemic stroke subtypes and their genetic basis: a comprehensive meta-analysis of small and large vessel stroke. Eur NeurolRao R. Tah V. Casas J. P. Hingorani A. Whittaker J. Smeeth L. Sharma P. 2009 61 2 76 86 - 21.
Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis. J Hum GenetBanerjee I. Veena Gupta. V. Ganesh S. 2007 52 3 205 219 - 22.
NeurologyMc Carron M. O. Delong D. MJ Alberts Apo. E. as genotype a. risk factor. for ischemic. cerebrovascular disease. a. meta-analysis 1999 53 6 1308 1311 - 23.
StrokeSudlow C. Martínez González. N. A. Kim J. Clark C. Does apolipoprotein. E. genotype influence. the risk. of ischemic. stroke intracerebral. hemorrhage or. subarachnoid hemorrhage?. Systematic review. meta-analyses of. . studies among. 59 cases 17,9 controls 2006 37 2 364 370 - 24.
Large-scale meta-anlysis of genetic studies in ischemic stroke: Five genes involving 152797 individuals. Indian J Hum GenetHamzi K. Tazzite A. Nadifi S. 2011 17 3 212 217 - 25.
Risk factors for cryptogenic ischaemic stroke. Eur J NeurolKarttunen V. Alfthan G. Hiltunen L. Rasi V. Kervinen K. Kesaniemi Y. A. Hillbom M. 2002 9 6 625 632 - 26.
Evaluation of the interactions of common genetic mutations in stroke subtypes. J NeurolSzolnoki Z. Somogyvári F. Kondacs A. Szabó M. Fodor L. 2002 249 10 1391 1397 - 27.
Evaluation of the modifying effects of unfavourable genotypes on classical clinical risk factors for ischaemic stroke. J Neurol Neurosurg PsychiatrySzolnoki Z. Somogyvári F. Kondacs A. Szabó M. Fodor L. Bene J. Melegh B. 2003 74 12 1615 1620 - 28.
Polymorphism in the P-selectin and interleukin-4 genes as determinants of stroke: a population-based, prospective genetic analysis. Hum Mol GenetZee R. Y. L. Cook N. R. Cheng S. Reynolds R. Erlich H. A. Lindpaintner K. Ridker P. M. 2004 13 4 389 396 - 29.
Cumulative effect of predisposing genotypes and their interaction with modifiable factors on the risk of ischemic stroke in young adults. StrokePezzini A. Grassi M. Del Zotto E. Archetti S. Spezi R. Vergani V. Assanelli D. Caimi L. Padovani A. 2005 36 3 533 539 - 30.
Candidate genetic risk factors of stroke: results of a multilocus genotyping assay. Clin ChemLalouschek W. Endler G. Schillinger M. Hsieh K. Lang W. Cheng S. Bauer P. Wagner O. Mannhalter C. 2007 53 4 600 605 - 31.
The glu298asp polymorphism in the nitric oxide synthase 3 gene is associated with the risk of ischemic stroke in two large independent case-control studies. Hum GenetBerger K. Stögbauer F. Stoll M. Wellmann J. Huge A. Cheng S. Kessler C. John U. Assmann G. Ringelstein E. B. Funke H. 2007 121 2 169 178 - 32.
Association studies of genetic polymorphism, environmental factors and their interaction in ischemic stroke. Neurosci LettGao X. Yang H. Zhi Ping. T. 2006 398 3 172 177 - 33.
Arterioscler Thromb Vasc BiolKessler C. Spitzer C. Stauske D. Mende S. Stadlmüller J. Walther R. Rettig R. The apolipoprotein. E. beta-fibrinogen G. A-4 gene polymorphisms. are associated. with ischemic. stroke involving. large-vessel disease. 1997 17 11 2880 2884 - 34.
Genetic risk for ischemic and hemorrhagic stroke. Arterioscler Thromb Vasc BiolYamada Y. Metoki N. Yoshida H. Satoh K. Ichihara S. Kato K. Kameyama T. Yokoi K. Matsuo H. Segawa T. Watanabe S. Nozawa Y. 2006 26 8 1920 1925 - 35.
Polymorphism of apoprotein E (APOE), methylenetetrahydrofolte reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. Clin Chem Lab MedTopić E. Šimundić A. M. Štefanović M. Demarin V. Vuković V. Lovrenčić-Huzjan A. Žuntar I. 2001 39 4 346 350 - 36.
McIlroy SP, Dynan KB, Lawson JT, Patterson CC, Passmore AP. Moderately elevated plasma homocysteine, methylenetetrahydrofolate reductase genotype, and risk for stroke, vascular dementia, and Alzheimer disease in Northern Ireland. Stroke2002 33 10 2351 2356 - 37.
Prevalence of apolipoprotein E phenotypes in patients with acute ischemic stroke. StrokeMahieux F. Bailleul S. Fenelon R. Couderc R. Laruelle P. Gunel M. 1990 I-115. - 38.
Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein (a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism. StrokePedro-Botet J. Sentí M. Nogues X. Rubiés-Prat J. Roquer J. D’Olhaberriague L. Olivé J. 1992 23 11 1556 1562 - 39.
Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A case-control study. StrokeCouderc R. Mahieux F. Bailleul S. Fenelon G. Mary R. Fermanian J. 1993 24 5 661 664 - 40.
StrokeCoria F. Rubio I. Nuñez E. Sempere A. P. Santa Engarcia. N. Bayón C. Cuadrado N. Apolipoprotein E. variants in. ischemic stroke. 1995 26 12 2375 2376 - 41.
Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis. Am J Hum GenetDe Andrade M. Thandi I. Brown S. Gotto A. Jr Patsch W. Boerwinkle E. 1995 56 6 1379 1390 - 42.
Arterioscler Thromb Vasc BiolKuusisto J. Mykkänen L. Kervinen K. Kesäniemi Y. A. Laakso M. Apolipoprotein E. phenotype is. not an. important risk. factor for. coronary heart. disease or. stroke in. elderly subjects. 1995 15 9 1280 1286 - 43.
StrokeBasun H. Corder E. H. Guo Z. Lannfelt L. Corder L. S. Manton K. G. Winblad B. Viitanen M. Apolipoprotein E. polymorphism stroke in. a. population sample. aged . years or. more 1996 27 8 1310 1315 - 44.
NeurolHachinski V. Graffagnino C. Beaudry M. Bernier G. Buck C. Donner A. JD Spence Doig. G. BM Wolfe Lipids. stroke a. paradox resolved. Arch 1996 53 4 303 308 - 45.
StrokeFerrucci L. Guralnik J. M. Pahor M. Harris T. Corti M. C. Hyman B. T. Wallace R. B. Havlik R. J. Apolipoprotein E. epsilon . allele risk of. stroke in. the older. population 1997 28 12 2410 2416 - 46.
Polymorphism of angiotensin converting enzyme, angiotensinogen, and apolipoprotein E genes in a Japanese population with cerebrovascular disease. Am J HypertensNakata Y. Katsuya T. Rakugi H. Takami S. Sato N. Kamide K. Ohishi M. Miki T. Higaki J. Ogihara T. 1997 Pt1):1391-1395. - 47.
Results of the Austrian Stroke Prevention Study. StrokeSchmidt R. Schmidt H. Fazekas F. Schumacher M. Niederkorn K. Kapeller P. Weinrauch V. Kostner G. M. Apolipoprotein E. polymorphism silent microangiopathy-related. cerebral damage. 1997 28 5 951 956 - 48.
The relationship between polymorphisms of apolipoprotein E gene and atherosclerotic cerebral infarction. Zhonghua Shen Jing Ge Za ZhiYang G. Jinjin G. Jianfei N. 1997 30 236 239 - 49.
Primary study of ApoE gene polymorphism in patients with cerebral infarction. Zhong Feng Yu Shen Jing Ji Bing Za ZhiDS Wang Jiang. L. Dai Y. M. 1997 14 71 74 - 50.
Zhu TB, Zhao SP, You XK. Effect of apolipoprotein E gene on plasma levels of lipids, lipoprotein, apolipoprotein and relation to cerebral infarction. Hu Nan Yi Xue1997 14 265 266 - 51.
Relationship between gene polymorphism of apolipoprotein E and serum lipids, lipoproteins, and apolipoproteins in Chinese patients with atherothrombotic brain infarction. Zhong Guo Shen Jing Mian Yi Xue He Shen Jing Bing Xue Za ZhiYan S. K. Zhou X. Li X. L. 1997 4 16 21 - 52.
Genetic risk factors and ischaemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme. Ann MedAalto-Setälä K. Palomäki H. Miettinen H. Vuorio A. Kuusi T. Raininko R. Salonen O. Kaste M. Kontula K. 1998 30 2 224 233 - 53.
Dement Geriatr Cogn DisordJi Y. Urakami K. Adachi Y. Maeda M. Isoe K. Nakashima K. Apolipoprotein E. polymorphism in. patients with. Alzheimer’s disease. vascular dementia. ischemic cerebrovascular. disease 1998 9 5 243 245 - 54.
Prevalence of apolipoprotein E alleles in healthy subjects and survivors of ischemic stroke: an Italian case-control study. StrokeMargaglione M. Seripa D. Gravina C. Grandone E. Vecchione G. Cappucci G. Merla G. Papa S. Postiglione A. Di Minno G. Fazio V. M. 1998 29 2 399 403 - 55.
The relationship between apolipoprotein E gene polymorphism and coronary heart disease and arteriosclerotic cerebral infarction. Zhonghua Yi Xue Yi Chuan Xue Za ZhiCao W. Chen F. Teng L. Wang S. Fu S. Zhang G. 1999 16 249 251 - 56.
Peng DQ, Zhao SP, Wang JL. Lipoprotein (a), and apolipoprotein E4 as independent risk factors for ischemic stroke. J Cardiovasc Risk1999 6 1 1 6 - 57.
Liu WG, Li ZH. The relationship between polymorphisms of apolipoprotein E gene and atherosclerotic cerebral infarction in middle-aged and young adults. Lin Chuang Shen Jing Bing Xue Za Zhi1999 12 134 136 - 58.
Peng DQ, Zhao SP. Comparison of apolipoprotein E genotype distribution in two types of stroke. Zhong Guo Dong Mai Ying Hua Za Zhi1999 7 34 36 - 59.
Acta Neurol ScandCatto A. J. Mc Cormack L. J. Mansfield M. W. Carter A. M. Bamford J. M. Robinson P. Grant P. J. Apolipoprotein E. polymorphism in. cerebrovascular disease. 2000 101 6 399 404 - 60.
Age-dependent association of apolipoprotein E genotypes with stroke subtypes in a Japanese rural population. StrokeKokubo Y. Chowdhury A. H. Date C. Yokoyama T. Sobue H. Tanaka H. 2000 31 6 1299 1306 - 61.
Prospective study of apolipoprotein E genotype and functional outcome following ischemic stroke. Arch NeurolMc Carron M. O. Muir K. W. Nicoll J. A. Stewart J. Currie Y. Brown K. Bone I. 2000 57 10 1480 1484 - 62.
Association between apolipoprotein E polymorphisms and cerebral stroke. Zhong Guo Shen Jing Jing Shen Ji Bing Za ZhiDing J. Zhu W. B. Fan W. 2000 26 371 372 - 63.
Wang TG, He ZY, Li YQ. The relation between apolipoprotein E gene polymorphism and atherosclerotic cerebral infarction. Yi Chuan2000 22 4 6 - 64.
J EpidemiolChowdhury A. H. Yokoyama T. Kokubo Y. MM Zaman Haque. A. Tanaka H. Apolipoprotein E. genetic polymorphism. stroke subtypes. in a. Bangladeshi hospital-based. study 2001 11 3 131 138 - 65.
NeurologyFrikke-Schmidt R. Nordestgaard B. G. Thudium D. Moes Grønholdt. M. L. Tybjaerg-Hansen A. Apo E. genotype predicts. A. D. other dementia. but not. ischemic cerebrovascular. disease 2001 56 2 194 200 - 66.
Lack of association between apolipoprotein E genoype and ischaemic stroke in a Scottish population. Eur J Clin InvestMac Leod. MJ De Lange R. P. Breen G. Meiklejohn D. Lemmon H. DS Clair 2001 31 7 570 573 - 67.
Lipid profile and apolipoprotein E genotyping in stroke: a case-control study. Neuroscience-NetSerteser M. Visvikis S. Ozben T. Herbeth B. Balkan S. Siest G. 2001 article 10015. - 68.
StrokeSlooter A. J. C. Bots M. L. Havekes L. M. del Sol A. I. Cruts M. Grobbee D. E. Hofman A. Van Broeckhoven C. Witteman J. C. van Dujn C. M. Apolipoprotein E. carotid artery. atherosclerosis the. Rotterdam study. 2001 32 9 1947 1952 - 69.
The relationship between polymorphisms of apolipoprotein E gene and cerebrovascular disorder. Xin Nao Xue Guan Bing Fang ZhiLi Y. W. He X. Zhao L. X. 2001 1 17 19 - 70.
Li ZH, LiuWG, Zhao XY, Chen YQ. Risk factor for stroke and ApoE polymorphism in the young and middle-aged. Cu Zhong Yu Shen Jing Ji Bing2001 8 326 329 - 71.
Clin GenetLuthra K. Prasad K. Kumar P. Dwivedi M. Pandey R. M. Das N. Apolipoprotein E. gene polymorphism. in cerebrovascular. disease a. case-control study. 2002 62 1 39 44 - 72.
Genet EpidemiolMorrison A. C. Ballantyne C. M. Bray M. Chambless L. E. Sharrett A. R. Boerwinkle E. L. P. L. polymorphism predicts. stroke risk. in men. 2002 22 3 233 242 - 73.
Shen LH, Ke KF, Li ZH. Research on apolipoprotein E gene polymorphism in patients with atherosclerotic cerebral infarction. Jiao Tong Yi Xue2002 16 504 505 - 74.
Association between apolipoprotein E polymorphism and lipid metabolism in patients with cerebral infarction. Zhong Guo Bing Li Sheng Li Za ZhiXia Y. Li H. L. Wang J. L. 2002 18 826 829 - 75.
The relation of apolipoprotein E gene polymorphism and cerebral infarction. Xue Shuan Yu Zhi Xue XueZhu L. Cui T. P. 2002 8 14 15 - 76.
AngiologyKolovou G. D. Daskalova D. Ch Hatzivassiliou. M. Yiannakouris N. Pilatis N. D. Elisaf M. Mikhailidis D. P. MA Cariolou Cokkinos. D. V. The epsilon. . alleles . of apolipoprotein. E. ischemic vascular. events in. the Greek. population-implications for. the interpretation. of similar. studies 2003 54 1 51 58 - 77.
J, Dembinska-Kiec A, Szczudlik A. LDL phenotype B and other lipid abnormalities in patients with large vessel disease and small vessel disease. J Neurol SciSlowik A. Iskra T. Turaj W. Hartwich J. Dembinska-Kiec A. Szczudlik A. L. D. L. phenotype B. other lipid. abnormalities in. patients with. large vessel. disease small vessel. disease 2003 - 78.
Souza DR, Campos BF, de Arruda EF, Yamamoto LJ, Trinidane DM, Tognola WA. Influence of the polymorphism of apolipoprotein E in cerebral vascular disease. Arq Neuropsiquiatr2003 61 1 7 13 - 79.
Um JY, Kim HM, Park HS, Joo JC, Kim KY, Kim YK, Hong SH. Candidate genes of cerebral infarction and traditional classification in Koreans with cerebral infarction. Int J Neurosci2005 115 6 743 756 - 80.
Shen Jing Ji Bing Yu Jing Shen Wei ShengWang X. T. Huang H. J. Ju K. Apolipoprotein E. gene polymorphism. in people. with cerebrovascular. disease in. the south. of the. Zhejiang province. 2003 3 17 19 - 81.
J NeurogenetDuzenli S. Pirim I. Gepdiremen A. Deniz O. Apolipoprotein E. polymorphism stroke in. a. population from. eastern Turkey. 2004 18 1 365 375 - 82.
Association of apolipoprotein E 4 polymorphism with cerebral infarction in Chinese Han population. Acta Pharmacol SinJin Z. Q. Fan Y. S. Ding J. Chen M. Fan W. Zhang G. J. Zhang B. H. Yu S. J. Zhang Y. S. Ji W. F. Zhang J. G. 2004 25 3 352 356 - 83.
NeuroepidemiologyLin H. F. Lai C. L. Tai C. T. Lin R. T. Liu C. K. Apolipoprotein E. polymorpshim in. ischemic cerebrovascular. diseases vascular dementia. patients in. Taiwan 2004 23 3 129 134 - 84.
Synergistic effect of apolipoprotein E polymorphisms and cigarette smoking on risk of ischemic stroke in young adults. StrokePezzini A. Grassi M. Zotto E. D. Bazzoli E. Archetti S. Assanelli D. Akkawi N. M. Albertini A. Padovani A. 2004 35 2 438 442 - 85.
Jugoslov Med BiohemStanković S. Jovanović-Marković Z. Majkić-Singh N. Stanković A. Glišić S. Živković M. Kostic V. Alavantic D. Apolipoprotein E. gene polymorphism. as risk a. factor for. ischemic cerebrovascular. disease 2004 23 3 255 264 - 86.
Cerebrovasc DisCerrato P. Baima C. Grasso M. Lentini A. Bosco G. Cassader M. Gambino R. Cavallo Perin. P. Pagano G. Fornengo P. Imperiale D. Bergamasco B. Bruno G. Apolipoprotein E. polymorphism stroke subtypes. in an. Italian cohort. 2005 20 4 264 269 - 87.
Association study of apolipoprotein e gene polymorphism and cerebral infarction in type 2 diabetic patients. Yi ChuanZhou J. Xue Y. L. Guan Y. X. Yang Y. D. Fu S. B. Zhang J. C. 2005 27 35 38 - 88.
Associations of apolipoprotein E exon 4 and lipoprotein lipase S447X polymorphisms with acute ischemic stroke and myocardial infarction. Clin Chem Lab MedBaum L. Ng H. K. Wong K. S. Tomlinson B. Rainer T. H. Chen X. Cheung W. S. Tang J. Tam W. W. S. Goggins W. Tong C. S. W. Kam D. Chan Y. Thomas G. N. Chook P. Woo K. S. 2006 44 3 274 281 - 89.
Kang SY, Lee WI. Apolipoprotein e polymorphism in ischemic stroke patients with different pathogenetic origins. Korean J Lab Med2006 26 3 210 216 - 90.
Relationship between polymorphism of apolipoprotein E gene and atherosclerotic cerebral infarction, hypertensive intracerebral hemorrhage in the youth. J Gannan Med UnivJiang Z. Q. Liu H. Zhang G. Z. 2006 26 331 334 - 91.
Wang JH, Ning XJ, Lu HY. The study on apolipoprotein E gene polymorphism characteristics of cerebral infarction and intracerebral hemorrhage. Zhong Guo Man Xing Bing Yu Fang Yu Kong Zhi2006 14 21 23 - 92.
J Int Med ResGiassakis G. Veletza S. Papanas N. Heliopoulos I. Piperidou H. Apolipoprotein E. first-ever ischaemic. stroke in. Greek hospitalized. patients 2007 35 1 127 133 - 93.
Lai CL, Liu CK, Lin RT, Tai CT. Association of apolipoprotein E polymorphism with ischemic stroke subtypes in Taiwan. Kaohsiung J Med Sci2007 23 10 491 497 - 94.
Parfenov MG, Nikolaeva TY, Sudomoina MA, Fedorova SA, Guekht AB, Gusev EI, Favorova OO. Polymorphism of apolipoprotein E (APOE) and lipoprotein lipase (LPL) genes and ischaemic stroke in individuals of Yakut ethnicity. J Neurol Sci2007 - 95.
Association of apolipoprotein E gene polymorphism with ischemic stroke involving large-vessel disease and its relation to serum lipid levels. J Stroke Cerebrovasc DisSaidi S. Slamia L. B. Ammou S. B. Mahjoub T. Almawi W. Y. 2007 16 4 160 166 - 96.
Associations of apolipoprotein E gene with ischemic stroke and intracranial atherosclerosis. Eur J Hum GenetAbboud S. Viiri L. E. Lütjohann D. Goebeler S. Luoto T. Friedrichs S. Desfontaines P. MD Gazagnes Laloux. P. Peeters A. Seeldrayers P. Lehtimaki T. Karhunen P. Pandolfo M. Laaksonen R. 2008 16 8 955 960 - 97.
Association and linkage disequilibrium analyses of APOE polymorphisms in atherosclerosis. Dis MarkersArtieda M. Gañán A. Cenarro A. García-Otín A. L. Jericó I. Civeira F. Pocoví M. 2008 24 2 65 72 - 98.
Association of apolipoprotein E genotype and cerebrovascular disease risk factors in a Turkish population. Int J NeurosciTasdemir N. Tamam Y. Toprak R. Tamam B. MS Tasdemir 2008 118 8 1109 1129 - 99.
Association of genetic variation in apolipoprotein E and low density lipoprotein receptor with ischemic stroke in Northern Han Chinese. J Neurol SciWang B. Zhao H. Zhou L. Dai X. Wang D. Cao J. Niu W. 2009 - 100.
Interaction of angiotensin-converting enzyme and apolipoprotein E gene polymorphisms in ischemic stroke involving large-vesssel disease. J Thromb ThrombolysisSaidi S. Zammiti W. Slamia L. B. Ammou S. B. Almawi W. Y. Mahjoub T. 2009 27 1 68 74 - 101.
J Neurol SciTascilar N. Dursun A. Ankarali H. Mungan G. Sumbuloglu V. Ekem S. Bozdogan S. Baris S. Aciman E. Cabuk F. Relationship of. apo E. polymorphism with. lipoprotein(a apo A. apo B. lipid levels. in atherosclerotic. infarct 2009 - 102.
StrokeMc Carron M. O. Muir K. W. Weir C. J. Dyker A. G. Bone I. Nicoll J. A. Lees K. R. The apolipoprotein. E. epsilon allele. outcome in. cerebrovascular disease. 1998 29 9 1882 1887 - 103.
Zhonghua Liu Xing Bing Xue Za ZhiWang L. Gu Y. Wu G. Wang W. Liu J. Liu J. Wu Z. A. case control. study on. the distribution. of apolipoprotein. A. I. gene polymorphisms. in the. survivors of. atherosclerosis cerebral. infarction 2000 21 22 25 - 104.
The relationship of apolipoprotein H G1025C (Try316Ser) polymorphism with stroke and its effect on plasma lipid levels in Changsha Hans. Zhonghua Yi Xue Yi Chuan Xue Za ZhiXia J. Yang Q. Yang Q. Xu H. Zhang L. 2003 20 114 118 - 105.
The relation between polymorphisms of apolipoprotein B gene and atherosclerotic cerebral infarction. Zhonghua Yi Xue Za ZhiWang L. Gu Y. Wu G. 1999 79 603 606 - 106.
Arch Biol SciStanković A. Stanković S. Jovanović-Marković Z. Zivković M. Djurić T. Glišić-Milosavljević S. Alavantić D. Apolipoprotein B. gene polymorphisms. in patients. from Serbia. with ischemic. cerebrovascular disease. 2007 59 4 303 309 - 107.
Association study between C7673T polymorphism in apolipoprotein B gene and cerebral infarction with family history in a Chinese population. Neurol IndiaZhang L. Zeng Y. Ma Yang M. Hu Q. Du Z. X. 2009 57 5 584 588 - 108.
Polymorphisms in apolipoprotein B and risk of ischemic stroke. J Clin Endocrinol MetabBenn M. Nordestgaard B. G. Jensen J. S. Tybjaerg-Hansen A. 2007 92 9 3611 3617 - 109.
J, Komlósi K, Maász A, Somogyvári F, Kondacs A, Szabó M, Fodor L, Bodor A, Melegh B. Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with elevated circulating triglyceride levels and confers susceptibility of ischemic stroke. J Mol NeurosciHavasi V. Szolnoki Z. Talián G. Bene J. Komlósi K. Maász A. Somogyvári F. Kondacs A. Szabó M. Fodor L. Bodor A. Melegh B. Apolipoprotein A. gene promoter. region T-11. polymorphism C. associates with. elevated circulating. triglyceride levels. confers susceptibility. of ischemic. stroke 2006 29 2 177 183 - 110.
Zhonghua Yi Xue Yi Chuam Xue Za ZhiLi J. Xu Zhu. X. Y. Association of. A. P. O. A. gene polymorphism. with levels. of lipids. atherosclerotic cerebral. infarction in. Chinese 2007 24 576 578 - 111.
The associated study on apolipoprotein A5 gene polymorphisms with carotid artherosclerosis in patients with cerebral infartion. Zhonghua Yi Xue Yi Chuan Xue Za ZhiZhang K. Qiu F. Li L. Gu G. Y. Tao Y. Wang L. Luo X. Y. Xia Y. Q. 2008 25 284 288 - 112.
Functional variants of glucokinase regulatory protein and apolipoprotein A5 genes in ischemic stroke. J Mol NeurosciJáromi L. Csöngei V. Polgár N. Szolnoki Z. Maász A. Horvatovich K. Faragó B. Sipeky C. Sáfrány E. Magyari L. Kisfali P. Mohás M. Janicsek I. Lakner L. Melegh B. 2010 41 1 121 128 - 113.
J NeurolMaász A. Kisfali P. Szolnoki Z. Hadarits F. Melegh B. Apolipoprotein A. gene C. variant G. confers risk. for the. development of. large-vessel associated. ischemic stroke. 2008 255 5 649 654 - 114.
Circ JMaasz A. Kisfali P. Jaromi L. Horvatovich K. Szolnoki Z. Csongei V. Safrany E. Sipeky C. Hadarits F. Melegh B. Apolipoprotein A. gene I. V. S. G4 allelic A. variant confers. susceptibility for. development of. ischemic stroke. 2008 72 7 1065 1070 - 115.
Association of apolipoprotein A5 gene promoter region-1131T>C with risk of stroke in Han Chinese. Eur J Intern MedLi X. Su D. Zhang X. Zhang C. 2011 22 1 99 102 - 116.
Single nucleotide polymorphisms in exons of the apo(a) kringles IV types 6 to 10 domain affect Lp(a) plasma concentrations and have different patterns in Africans and Caucasians. Hum Mol GenetOgorelkova M. Kraft H. G. Ehnholm C. Utermann G. 2001 10 8 815 824 - 117.
J Clin InvestTrommsdorff M. Köchl S. Lingenhel A. Kronenberg F. Delport R. Vermaak H. Lemming L. Klausen I. C. Faergeman O. Utermann G. Kraft H. G. A. pentanucleotide repeat. polymorphism in. the 5’. control region. of the. apolipoprotein (a. gene is. associated with. lipoprotein (a. plasma concentrations. in Caucasians. 1995 96 1 150 157 - 118.
Relationship between pentanucleotide repeat polymorphism of apolipoprotein (a) gene and atherosclerosis cerebral infarction in Han nationality. Zhonghua Shen Jing Ge Za ZhiHu B. Zhou X. Shao H. 2000 33 172 175 - 119.
Relation of pentanucleotide repeat polymorphism of apolipoprotein (a) gene to plasma lipoprotein (a) level among Chinese patients with myocardial infarction and cerebral infarction. Zhonghua Yi Xue Za ZhiLiu X. Sun L. Li Z. Gao Y. Hui R. 2002 82 1396 1400 - 120.
StrokeSun L. Li Z. Zhang H. Ma Liao A. Wang Y. Zhao D. Zhu B. Zhao Z. Zhang J. Wang Z. Hui W. Pentanucleotide R. repeat T. T. T. T. A. polymorphism of. apolipoprotein(a gene. plasma lipoprotein(a. are associated. with ischemic. hemorrhagic stroke. in Chinese. a. multicenter case-control. study in. China 2003 34 7 1617 1622 - 121.
Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J MedClarke R. Peden J. F. Hopewell J. C. Kyriakou T. Goel A. Heath S. C. Parish S. Barlera S. Franzosi M. G. Rust S. Bennett D. Silveira A. Malarstig A. Green F. R. Lathrop M. Gigante B. Leander K. de Faire U. Seedorf U. Hamsten A. Collins R. Watkins H. Farrall M. 2009 361 26 2518 2528 - 122.
StrokeWang X. Cheng S. Brophy V. H. Erlich H. A. Mannhalter C. Berger K. Lalouschek W. Browner W. S. Shi Y. Ringelstein E. B. Kessler C. Luedemann J. Lindpaintner K. Liu L. Ridker P. M. Zee R. Y. Cook N. R. A. meta-analysis of. candidate gene. polymorphisms ischemic stroke. in . study populations. association of. lymphotoxin-alpha in. nonhypertensive patients. 2009 40 3 683 695 - 123.
Lipoprotein(a) genetic variants associated with coronary and peripheral vascular disease but not with stroke risk in the Heart Protection Study. Circ Cardiovasc GenetHopewell J. C. Clarke R. Parish S. Armitage J. Lathrop M. Hager J. Collins R. Heart Protection. Study Collaborative. Group 2011 4 1 68 73 - 124.
Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. AtherosclerosisChasman D. I. Shiffman D. Zee R. Y. Louie J. Z. MM Luke Rowland. C. M. Catanese J. J. Buring J. E. Devlin J. J. Ridker P. M. 2009 203 2 371 376 - 125.
Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study. Arterioscler Thromb Vasc BiolOrdovas J. M. Cupples L. A. Corella D. JD Otvos Osgood. D. Martinez A. Lahoz C. Coltell O. Wilson P. W. Schaefer E. J. 2000 20 5 1323 1329 - 126.
Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial. Arterioscler Thromb Vasc BiolME Brousseau O’Connor. J. J. Jr Ordovas J. M. Collins D. JD Otvos Massov. T. Mc Namara J. R. Rubins H. B. Robins S. J. Schaefer E. J. 2002 22 7 1148 1154 - 127.
The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group. N Engl J MedKuivenhoven J. A. Jukema J. W. Zwinderman A. H. de Knijff P. Mc Pherson R. Bruschke A. V. Lie K. I. Kastelein J. J. 1998 338 2 86 93 - 128.
Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study. AtherosclerosisElosua R. Cupples L. A. Fox C. S. Polak J. F. D’Agostino R. A. Sr Wolf P. A. O’Donnell C. J. Ordovas J. M. 2006 189 1 222 228 - 129.
Cholesteryl ester transfer protein polymorphism associated with macroangiopathy in Japanese patients with type 2 diabetes. AtherosclerosisMeguro S. Takei I. Murata M. Hirose H. Takei N. Mitsuyoshi Y. ishii K. Oguchi S. Shinohara J. Takeshita E. Watanabe K. Saruta T. 2001 156 1 151 156 - 130.
Asselbergs FW, Moore JH, van den Berg MP, Rimm EB, de Boer RA, Dullaart RP, Navis G, van Gilst WH. A role for CETP TaqIB polymorphism in determining susceptibility to atrial fibrillation: a nested case control study. BMC Med Genet 2006;7:39. - 131.
Cholesteryl ester transfer protein levels and gene deficiency in Chinese patients with cardio-cerebrovascular diseases. Chin Med J (Engl)Zhuang Y. Wang J. Qiang H. Li Y. Liu X. Li L. Chen G. 2002 115 3 371 374 - 132.
Cholesterlyl ester transfer protein TaqI B and lipoprotein lipase Ser447Ter gene polymorphisms are not associated with ischaemic stroke in Greek patients. Neurosci LettFidani L. Hatzitolios A. I. Goulas A. Savopoulos C. Basayannis C. Kotsis A. 2005 - 133.
J Int MedQuarta G. Stanzione R. Evangelista A. Zanda B. Sciarretta S. Di Angelantonio E. Marchitti S. Di Murro D. Volpe M. Rubattu S. A. protective role. of a. cholesteryl ester. transfer protein. gene variant. towards ischaemic. stroke in. Sardinians 2007 262 5 555 561 - 134.
Cholesterol ester transfer protein, interleukin-8, peroxisome proliferator activator receptor alpha, and toll-like receptor 4 genetic variations and risk of incident nonfatal myocardial infarction and ischemic stroke. Am J CardiolEnquobahrie D. A. Smith N. L. Bis J. C. Carty C. L. Rice K. M. Lumley T. Hindorff L. A. RN Lemaitre Williams. DS Siscovick Heckbert. S. R. BM Psaty 2008 101 12 1683 1688 - 135.
Common genetic variation in six lipid-related and statin-related genes, statin use and risk of incident nonfatal myocardial infarction and stroke. Pharmacogenet GenomicsHindorff L. A. RN Lemaitre Smith. N. L. Bis J. C. Marciante K. D. Rice K. M. Lumley T. Enquobahrie D. A. Li G. Heckbert S. R. BM Psaty 2008 18 8 677 682 - 136.
High density lipoproteins and atherosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arterioscler Thromb Vasc BiolVon Eckardstein. A. Nofer J. R. Assman G. 2001 21 1 13 27 - 137.
Braunham LR, Singaraja RR, Hayden MR. Variations on a gene: rare and common variants in ABCA1 and their impact on HDL cholesterol levels and atherosclerosis. Annu Rev Nutr2006 26 105 129 - 138.
Decreased frequencies of ABCA1 polymorphisms R219K andAndrikovics H. Pongrácz E. Kalina E. Szilvási A. Aslanidis C. Schmitz G. Tordai I. 771M in Hungarian patients with cerebrovascular and cardiovascular diseases. Cerebrovasc Dis2006 - 139.
The effect of ABCA1 gene polymorphisms on ischaemic stroke risk and relationship with lipid profile. BMC Med GeneticsPasdar A. Yadegarfar G. Cumming A. Whalley L. St Clair. D. Mac Leod. MJ 2007 8 30 36 - 140.
Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals. StrokeYamada Y. Metoki N. Yoshida H. Satoh K. Kato K. Hibino T. Yokoi K. Watanabe S. Ichihara S. Aoyagi Y. Yasunaga A. Park H. Tanaka M. Nozawa Y. 2008 39 8 2211 2218 - 141.
Structure and evolution of the lipase superfamily. J Lipid ResHide W. A. Chan L. Li W. H. 1992 33 2 167 178 - 142.
Mead JR, Irvine SA, Ramji DP. Lipoprotein lipase: structure, function, regulation, and role in disease. J Mol Med2002 80 12 753 769 - 143.
Goldberg IJ. Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. J Lipid Res1996 37 4 693 707 - 144.
Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions. Proc Natl Acad Sci USAYla-Herttuala S. BA Lipton Rosenfeld. ME Goldberg I. J. Steinberg D. Witztum J. L. 1991 88 22 10143 10147 - 145.
Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques. J Clin InvestO’Brien K. D. Gordon D. Deeb S. Ferguson M. Chait A. 1992 89 5 1544 1550 - 146.
The role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins by macrophages. J Biol ChemLindqvist P. Ostlund-Lindqvist A. M. Witztum J. L. Steinberg D. Little J. A. 1983 258 15 9086 9092 - 147.
Mead JR, Ramji DP. The pivotal role of lipoprotein lipase in atherosclerosis. Cardiovasc Res2002 55 2 261 269 - 148.
A, Nordestgaard BG. Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. CirculationWittrup H. H. Tybjaerg-Hansen A. Nordestgaard B. G. Lipoprotein lipase. mutations plasma. lipids lipoproteins risk of. ischemic heart. disease 1999 99 22 2901 2907 - 149.
Two common mutations (D9N, N291S) in lipoprotein lipase: a cumulative analysis of their influence on plasma lipids and lipoproteins in men and women. Clin GenetKastelein J. J. Ordovas J. M. ME Wittekoek Pimstone. S. N. Wilson W. F. Gagné S. E. Larson M. G. Schaefer E. J. Boer J. M. Gerdes C. Hayden M. R. 1999 56 4 297 305 - 150.
AtherosclerosisChamberlain J. C. Thorn J. A. Oka K. Galton D. J. Stocks J. D. N. A. polymorphisms at. the lipoprotein. lipase gene. associations in. normal hypertriglyceridaemic subjects. 1989 79 1 85 91 - 151.
Polymorphisms in the lipoprotein lipase gene and their associations with plasma lipid concentrations in 40-year-old Danish men. CirculationGerdes C. Gerdes L. U. Hansen P. S. Faergeman O. 1995 92 7 1765 1769 - 152.
Polymorphism of the lipoprotein lipase gene and risk of atherothrombotic cerebral infarction in the Japanese. StrokeShimo-Nakanishi Y. Urabe T. Hattori N. Watanabe Y. Nagao T. Yokochi M. Hamamoto M. Mizuno Y. 2001 32 7 1481 1486 - 153.
StrokeWang X. Cheng S. Brophy V. H. Erlich H. A. Mannhalter C. Berger K. Lalouschek W. Browner W. S. Shi Y. Ringelstein E. B. Kessler C. Luedemann J. Lindpaintner K. Liu L. Ridker P. M. Zee R. Y. Cook N. R. A. meta-analysis of. candidate gene. polymorphisms ischemic stroke. in . study populations. association of. lymphotoxin-alpha in. nonhypertensive patients. 2009 40 3 683 95 - 154.
Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: A meta-analysis. Thromb ResWang C. Sun T. Li H. Bai J. Li Y. 2011 e107 e112. - 155.
Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J MedCummings S. R. Nevitt M. C. Browner W. S. Stone K. Fox K. M. Ensrud K. E. Cauley J. Black D. Vogt T. M. 1995 332 12 767 773 - 156.
Zhongguo Yi Xue Ke Xue Yuan Xue BaoZhao Y. Ma Liu L. Y. Wang Y. X. Liu X. Y. Lindpaintner L. S. Relationship K. between-E alpha. Na C. gene Thr6. Ala polymorphism. ischemic stroke. 2001 23 499 501 - 157.
Lipoprotein lipase gene polymorphisms in ischaemic stroke and carotid stenosis. Eur J Clin InvestHuang P. Kostulas K. Huang W. X. Crisby M. Kostulas V. Hillert J. 1997 27 9 740 742 - 158.
CirculationWittrup H. H. Nordestgaard B. G. Sillesen H. Schnohr P. Tybjaerg-Hansen A. A. common mutation. in lipoprotein. lipase confers. a. 2-fold increase. in risk. of ischemic. cerebrovascular disease. in women. but not. in men. 2000 101 20 2393 2397 - 159.
Association of lipoprotein lipase Ser447Ter polymorphism with brain infarction: a population-based neuropathological study. Ann MedMyllykangas L. Polvikoski T. Sulkava R. Notkola I. L. Rastas S. Verkkoniemi A. Tienari P. J. Niinistö L. Hardy J. Pérez-Tur J. Kontula K. Haltia M. 2001 33 7 486 492 - 160.
The lipoprotein lipase Ser447Ter mutation and risk of stroke in the Chinese. Clin Chim ActaZhao S. P. Tong Q. G. Xiao Z. J. Cheng Y. C. Zhou H. N. Nie S. 2003 - 161.
Associations between Ser447Ter gene polymorphism of lipoprotein lipase and atherosclerotic cerebral infarction. Zhonghua Yi Xue Yi Chuan Xue Za ZhiGuan G. D. Xu E. Wang X. J. Xu Y. H. Qiu S. D. 2006 23 519 522 - 162.
Genetic profile of ischemic cerebrovascular disease and carotid stenosis. Acta Neurol ScandKostulas K. Brophy V. H. Moraitis K. Manolescu A. Kostulas V. Gretarsdottir S. Cheng S. Hillert J. 2008 118 3 146 152 - 163.
Polymorphisms of the lipoprotein lipase gene are associated with atherosclerotic cerebral infarction in the Chinese. NeuroscienceXu E. Li W. Zhan L. Guan G. Wang X. Chen S. Shi Y. 2008 155 2 403 408 - 164.
Genetic epidemiological study on discordant sib pairs of ischemic stroke in Beijing Fangshan District. Beijing Da Xue Xue BaoTang X. Zhu Y. P. Li N. Chen D. F. Zhang Z. X. Dou H. D. Hu Y. H. 2007 39 119 125 - 165.
Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for Its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc BiolAviram M. Billecke S. Sorenson R. Bisgaier C. Newton R. Rosenblat M. Erogul J. Hsu C. Dunlop C. La Du B. 1998 18 10 1617 1624 - 166.
Autoantibody against oxidised LDL and progression of carotid atherosclerosis. LancetSalonen J. T. Ylä-Herttuala S. Yamamoto R. Butler S. Korpela H. Salonen R. Nyyssönen K. Palinski W. Witztum J. L. 1992 339 8798 883 887 - 167.
The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. GenomicsPrimo-Parmo S. L. Sorenson R. C. Teiber J. La Du B. N. 1996 33 3 498 507 - 168.
Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin InvestWatson A. D. Berliner J. A. Hama S. Y. La Du B. N. Faull K. F. Fogelman A. M. Navab M. 1995 96 6 2882 2891 - 169.
Arterioscler Thromb Vasc BiolReddy S. T. Wadleigh D. J. Grijalva V. Ng C. Hama S. Gangopadhyay A. Shih D. M. Lusis A. J. Navab M. Fogelman A. M. Human paraoxonase. is an. H. D. L-associated enzyme. with biological. activity similar. to paraoxonase. protein but. is not. regulated by. oxidized lipids. 2001 21 4 542 547 - 170.
J, Wadleigh DJ, Gangopadhyay A, Hama S, Grijalva VR, Navab M, Fogelman AM, Reddy ST. Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol ChemNg C. J. Wadleigh D. J. Gangopadhyay A. Hama S. Grijalva V. R. Navab M. Fogelman A. M. Reddy S. T. Paraoxonase is a. ubiquitously expressed. protein with. antioxidant properties. is capable. of preventing. cell-mediated oxidative. modification of. low density. lipoprotein 2001 276 48 44444 44449 - 171. Mackness M, Mackness B. Paraoxonase 1 and atherosclerosis: is the gene or the protein more important? Free Radic Biol Med 2004;37(9):1317-1323.
- 172.
Four paraoxonase gene polymorphisms in 11212 cases of coronary heart disease and 12786 controls: meta-analysis of 43 studies. LancetWheeler J. G. BD Keavney Watkins. H. Collins R. Danesh J. 2004 363 9410 689 695 - 173.
The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women’s Heart and Health cohort study and a meta-analysis. BMC GenetLawlor D. A. Day I. N. Gaunt T. R. Hinks L. J. Briggs P. J. Kiessling M. Timpson N. Smith G. D. Ebrahim S. 2004 - 174.
Genet MedDahabreh I. J. Kitsios G. D. Kent D. M. Trikalinos T. A. Paraoxonase . polymorphisms ischemic stroke. risk A. systematic review. meta-analysis 2010 12 10 606 615 - 175.
Relationship between Paraoxonase 1 (PON1) gene polymorphisms and susceptibility of stroke: a meta-analysis. Eur J EpidemiolBanerjee I. 2010 25 7 449 458 - 176.
Lack of association between carotid intima-media thickness and paraoxonase gene polymorphism in non-insulin dependent diabetes mellitus. AtherosclerosisCao H. Girard-Globa A. Serusclat A. Bernard S. Bondon P. Picard S. Berthezene F. Moulin P. 1998 138 2 361 366 - 177.
Evidence for association between paraoxonase gene polymorphisms and atherosclerotic diseases. AtherosclerosisImai Y. Morita H. Kurihara H. Sugiyama T. Kato N. Ebihara A. Hamada C. Kurihara Y. Shindo T. Oh-hashi Y. Yazaki Y. 2000 149 2 435 442 - 178.
StrokeVoetsch B. Benke K. S. Damasceno B. P. Siqueira L. H. Loscalzo J. Paraoxonase 1. Gln--> Arg. polymorphism an. independent risk. factor for. nonfatal arterial. ischemic stroke. among young. adults 2002 33 6 1459 1464 - 179.
Med Sci MonitUeno T. Shimazaki E. Matsumoto T. Watanabe H. Tsunemi A. Takahashi Y. Mori M. Hamano R. Fujioka T. Soma M. Matsumoto K. Kanmatsuse K. Paraoxonase polymorphism. Leu-Met is associated. with cerebral. infarction in. Japanese populations. 2003 CR208 CR212. - 180.
Chen JH, Zeng QX. Relationship between the paraoxonase gene 192 polymorphism and atherosclerotic cerebral infarction. Zhong Guo Lin Chuang Kang Fu2003 7 3036 3037 - 181.
Evaluation of the paraoxonases as candidate genes for stroke: Gln192Arg polymorphism in the paraoxonse 1 gene is associated with increased risk of stroke. StrokeRanade K. Kirchgessner T. G. Iakoubova O. A. Devlin J. J. Del Monte T. Vishnupad P. Hui L. Tsuchihashi Z. Sacks F. M. MS Sabatine Braunwald. E. White T. J. Shaw P. M. Dracopoli N. C. 2005 36 11 2346 2350 - 182.
The association of PON1 Q192R gene polymorphism with atherosclerotic cerebral infarction. Zhong Hua Shen Jing Ke Za ZhiHuang Q. Liu Y. H. Yang Q. 2005 38 454 455 - 183.
The relationship between PON1-192 polymorphism and type of cerebral infarction. Nao Yu Shen Jing Ji Bing Za ZhiWu J. Zhao S. P. Tan L. M. 2005 13 253 255 - 184.
The relationship between paraoxonase gene 192Gln/Arg polymorphism and ischemic cerebrovascular disease. Zhong Hua Lao Nian Xin Nao Xue Guan Bing Za ZhiYu L. T. Yu D. C. Li L. 2005 7 254 256 - 185.
Clin BiochemBaum L. Ng H. K. Woo K. S. Tomlinson B. Rainer T. H. Chen X. Cheung W. S. Chan D. K. Thomas G. N. Tong C. S. Wong K. S. Paraoxonase . gene Q1. polymorphism R. affects stroke. myocardial infarction. risk 2006 39 3 191 195 - 186.
Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in Chinese Han population. Neurol ResHuang Q. Liu Y. H. Yang Q. D. Xiao B. Ge L. Zhang N. Xia J. Zhang L. Liu Z. J. 2006 28 5 549 554 - 187.
Paraoxonase gene polymorphism and haplotype analysis in a stroke population. BMC Medical GeneticsPasdar A. Ross-Adams H. Cumming A. Cheung J. Whalley L. St Clair. D. Mac Leod. MJ 2006 7 28 33 - 188.
IUBMB LifeAydin M. Gencer M. Cetinkaya Y. Ozkok E. Ozbek Z. Kilic G. Orken C. Tireli H. Kara I. P. O. N. 55/1 polymorphism oxidative. stress type. prognosis severity of. stroke I. U. B. M. 2006 58 3 165 172 - 189.
Chen WR, Xiao ZJ, Zhao SQ. The relationship between the gene polymorphism in paraoxonase and lacunar infarction. Cu Zhong Yu Shen Jing Ji Bing2006 13 75 78 - 190.
Acta Neurol ScandSchiavon R. Turazzini M. De Fanti E. Battaglia P. Targa L. Del Colle R. Fasolin A. Silvestri M. Biasioli S. Guidi G. P. O. N. activity genotype in. patients with. arterial ischemic. stroke in healthy. individuals 2007 116 1 26 30 - 191.
Shin BS, Oh SY, Kim YS, Kim KW. The paraoxonase gene polymorphism in stroke patients and lipid profile. Acta Neurol Scand2008 117 4 237 243 - 192.
Cerebrovasc DisSlowik A. Wloch D. Szermer P. Wolkow P. Malecki M. Pera J. Turaj W. Dziedzic T. Klimkowicz-Mrowiec A. Kopec G. Figlewicz D. A. Szczudlik A. Paraoxonase . gene C3. polymorphism S. is associated. with a. risk of. large vessel. disese stroke. in a. Polish population. 2007 - 193.
Clin BiochemCan Demirdöğen. B. Türkanoğlu A. Bek S. Sanisoğlu Y. Demirkaya S. Vural O. Arinç E. Adali O. Paraoxonase/arylesterase ratio. P. O. N. 1. polymorphism Q. R. status P. O. N. are associated. with increased. risk of. ischemic stroke. 2008 - 194.
Analysis of paraoxonase 1 (PON1) genetic polymorphisms and activities as risk factors for ischemic stroke in Turkish population. Cell Biochem FunctDemirdöğen B. C. Demirkaya S. Türkanoğlu A. Bek S. Arınç E. Adali O. 2009 27 8 558 567 - 195.
Lack of association between the paraoxonase 1 Q/R192 single nucleotide polymorphism and stroke in a Chinese cohort. Acta Neurol BelgXiao Z. J. Chen J. Sun Y. Zheng Z. J. 2009 109 3 205 209 - 196.
Arterioscler Thromb Vasc BiolSchmidt R. Schmidt H. Fazekas F. Kapeller P. Roob G. Lechner A. Kostner G. M. Hartung H. P. M. R. I. cerebral white. matter lesions. paraoxonase P. O. N. polymorphisms three-year. follow-up of. the Austrian. Stroke Prevention. Study 2000 20 7 1811 1816 - 197.
The combined effect of paraoxonase promoter and coding region polymorphisms on the risk of arterial ischemic stroke among young adults. Arch NeurolVoetsch B. Benke K. S. Panhuysen C. I. Damasceno B. P. Loscalzo J. 2004 61 3 351 356 - 198.
Genetic polymorphisms of Chinese patients with ischemic stroke and concurrent stenoses of extracranial and intracranial vessels. J Clin NeurosciMan B. L. Baum L. Fu Y. P. Chan Y. Y. Lam W. Hui C. F. Leung W. H. Wong K. S. 2010 17 10 1244 1247 - 199.
Relationship between single nucleotide polymorphisms of paraoxonase 2 and stroke. Zhonghua Yi Xue Yi Chuan Xue Za ZhiXu H. W. Zhao Z. Yuan N. Xiao B. Yang X. S. BS Tang 2007 24 328 330 - 200.
Paraoxonase gene polymorphisms and stroke severity. Eur J NeurolLazaros L. Markoula S. Kyritsis A. Georgiou I. 2010 17 5 757 759 - 201.
Relationship between the Nco I, Ava II polymorphism of low density lipoprotein receptor gene and atherosclerotic cerebral infarction. Zhonghua Yi Xue Yi Chuan Xue Za ZhiGuo Y. Guo J. Zheng D. Pan L. Li Q. Ruan G. 2002 19 209 212 - 202.
Single nucleotide polymorphism in the low-density lipoprotein receptor is associated with a threefold risk of stroke. A case-control and prospective study. Eur Heart JFrikke-Schmidt R. Nordestgaard B. G. Schnohr P. Tybjærg-Hansen A. 2004 25 11 943 951 - 203.
Genetic polymorphisms of low density lipoprotein receptor can modify stroke presentation. Neurol Res.JD Lee Lin. Y. H. Hsu H. L. Huang Y. C. Wu C. Y. Ryu S. J. Lee M. Huang Y. C. Hsiao M. C. Chang Y. J. Chang C. H. Lee T. H. 2010 32 5 535 540 - 204.
Association study between three polymorphisms and myocardial infarction and ischemic stroke in Chinese Han population. Thromb ResYang X. C. Zhang Q. Li S. J. Wan X. H. Zhong G. Z. Hu W. L. Li L. Yu S. Z. Jin L. Wang X. F. 2010 126 4 292 294 - 205.
Brain ResHattori H. Sonoda A. Sato H. Ito D. Tanahashi N. Murata M. Saito I. Watanabe K. Suzuki N. G5 polymorphism C. of oxidized. L. D. L. receptor geen. . O. L. R. ischemic stroke. 2006 1121 1 246 249 - 206.
Genet Test Mol BiomarkersVietri M. T. Molinari A. M. Boggia M. Parisi M. Cioffi M. S4- I. V. A. G. S4- I. V. polymorphisms C. T. in O. L. R. gene in. patients with. ischemic cerebrovascular. diseases 2010 14 1 9 11 - 207.
Imig JD, Navar LG, Roman RJ, Reddy KK, Falck JR. Actions of epoxygenase metabolites on the preglomerular vasculature. J Am Soc Nephrol1996 7 11 2364 2370 - 208.
Heizer ML, McKinney JS, Ellis EF. Epoxyeicosatrienoic acid inhibits platelet aggregation in mouse cerebral arterioles. Stroke1991 22 11 1389 1393 - 209.
Membrane-potential-dependent inhibition of platelet adhesion to endothelial cells by epoxyeicosatrienoic acids. Arterioscler Thromb Vasc BiolKrötz F. Riexinger T. MA Buerkle Nithipatikom. K. Gloe T. Sohn H. Campbell W. B. Pohl U. 2004 24 3 595 600 - 210.
Soluble epoxide hydrolase gene deletion is protective against experimental cerebral ischemia. StrokeZhang W. Otsuka T. Sugo N. Ardeshiri A. Alhadid Y. K. Iliff J. J. De Barber A. E. Koop D. R. Alkayed N. J. 2008 39 7 2073 2078 - 211.
Genetic variation in cytochromeZhang L. Ding H. Yan J. Hui R. Wang W. Kissling G. E. Zeldin D. C. Wang D. W. 450 J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population. PharmacogenetGenomics2008 - 212.
The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke. Hum Mol GenetFornage M. Lee C. R. Doris P. A. MS Bray Heiss. G. Zeldin D. C. Boerwinkle E. 2005 14 19 2829 2837 - 213.
Prog Lipid ResNewman J. W. Morisseau C. BD Hammock Epoxide. hydrolases their. roles interactions with. lipid metabolism. 2005 44 1 1 51 - 214.
Soluble epoxide hydrolase variant (Glu287Arg) modifies plasma total cholesterol and triglyceride phenotype in familial hypercholesterolemia: intrafamilial association study in an eight-generation hyperlipidemic kindred. J Hum GenetSato K. Emi M. Ezura Y. Fujita Y. Takada D. Ishigami T. Umemura S. Xin Y. Wu L. L. Larrinaga-Shum S. Stephenson S. H. Hunt S. C. Hopkins P. N. 2004 49 1 29 34 - 215.
Polymorphism in human soluble epoxide hydrolase. J Mol PharmacolBD Przybyla-Zawislak Srivastava. P. K. Vázquez-Matiás H. et al. 2003 64 2 482 490 - 216.
The soluble epoxide hydrolase gene harbors sequence variation associated with susceptibility to and protection from incident ischemic stroke. Hum Mol GenetFornage M. Lee C. R. Doris P. A. MS Bray Heiss. G. Zeldin D. C. Boerwinkle E. 2005 14 19 2829 2837 - 217.
Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with an increased risk of ischemic stroke in white Europeans. StrokeGschwendtner A. Ripke S. Freilinger T. Lichtner P. Müller-Myhsok B. Wichmann H. Meitinger T. Dichgans M. 2008 39 5 1593 1596 - 218.
Genetic variation in cytochromeZhang L. Ding H. Yan J. Hui R. Wang W. Kissling G. E. Zeldin D. C. Wang D. W. 450 J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population. Pharmacogenet Genomics2008 - 219.
Identification and functional characterization of human soluble epoxide hydrolase genetic polymorphisms. J Biol ChemSandberg M. Hassett C. Adman E. T. Meijer J. Omiecinski C. J. 2000 275 37 28873 28881 - 220.
Genetically reduced soluble epoxide hydrolase activity and risk of stroke and other cardiovascular disease. StrokeLee J. Dahl M. Grande P. Tybjaerg-Hansen A. Nordestgaard B. G. 2010 - 221.
Homozygosity for the EPHX2 K55R polymorphism increases the long-term risk of ischemic stroke in men: a study in Swedes. Pharmacogenet GenomicsFava C. Montagnana M. Danese E. Almgren P. Hedblad B. Engström G. Berglund G. Minuz P. Melander O. 2010 20 2 94 103 - 222.
Wang WYS, Barratt BJ, Clayton DG, Todd JA. Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet2005 6 2 109 118 - 223.
Wellcome Trust Case Control Consortium. Genomewide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature2007 447 7145 661 678 - 224.
Lancet NeurolMatarin M. Brown W. M. Scholz S. Simon-Sanchez J. Fung H. C. Hernandez D. Gibbs J. R. De Vrieze F. W. Crews C. Britton A. Langefeld C. D. Brott T. G. Brown R. D. Jr Worrall B. B. Frankel M. Silliman S. Case L. D. Singleton A. Hardy J. A. Rich S. S. Meschia J. F. A. genome-wide genotyping. study in. patients with. ischaemic stroke. Initial analysis. data release. 2007 6 5 414 420 - 225.
Genomewide association studies of stroke. N Engl J MedMA Ikram Seshadri. S. Bis J. C. Fornage M. De Stefano A. L. Aulchenko Y. S. Debette S. Lumley T. Folsom A. R. van den Herik. E. G. MJ Bos Beiser. A. Cushman M. Launer L. J. Shahar E. Struchalin M. Du Y. Glazer N. L. Rosamond W. D. Rivadeneira F. Kelly-Hayes M. Lopez O. L. Coresh J. Hofman A. De Carli C. Heckbert S. R. Koudstaal P. J. Yang Q. Smith N. L. Kase C. S. Rice K. Haritunians T. Roks G. de Kort P. L. Taylor K. D. de Lau L. M. BA Oostra Uitterlinden. A. G. Rotter J. I. Boerwinkle E. BM Psaty Mosley. T. H. van Duijn C. M. MM Breteler Longstreth. W. T. Jr Wolf P. A. 2009 360 17 1718 1728 - 226.
Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. Ann NeurolGretarsdottir S. Thorleifsson G. Manolescu A. Styrkarsdottir U. Helgadottir A. Gschwendtner A. Kostulas K. Kuhlenbaumer G. Bevan S. Jonsdottir T. Bjarnason H. Saemundsdottir J. Palsson S. DO Arnar Holm. H. Thorgeirsson G. Valdimarsson E. M. Sveinbjornsdottir S. Gieger C. Berger K. Wichmann H. E. Hillert J. Markus H. Gulcher J. R. Ringelstein E. B. Kong A. Dichgans M. Gudbjartsson D. F. Thorsteinsdottir U. Stefansson K. 2008 64 4 402 409 - 227.
Nat GenetGudbjartsson D. F. Holm H. Gretarsdottir S. Thorleifsson G. Walters G. B. Thorgeirsson G. Gulcher J. Mathiesen E. B. Njolstad I. Nyrnes A. Wilsgaard T. Hald E. M. Hveem K. Stoltenberg C. Kucera G. Stubblefield T. Carter S. Roden D. Ng M. C. Baum L. So W. Y. Wong K. S. Chan J. C. Gieger C. Wichmann H. E. Gschwendtner A. Dichgans M. Kuhlenbaumer G. Berger K. Ringelstein E. B. Bevan S. Markus H. S. Kostulas K. Hillert J. Sveinbjornsdottir S. Valdimarsson E. M. Lochen M. L. Ma Darbar R. C. Kong D. Arnar A. DO Thorsteinsdottir U. Stefansson K. A. sequence variant. in zfhx. on 16q. associates with. atrial fibrillation. ischemic stroke. 2009 41 8 876 878 - 228.
Nat GenetKubo M. Hata J. Ninomiya T. Matsuda K. Yonemoto K. Nakano T. Matsushita T. Yamazaki K. Ohnishi Y. Saito S. Kitazono T. Ibayashi S. Sueishi K. Iida M. Nakamura Y. Kiyohara Y. A. nonsynonymous snp. in prkch. (protein kinase. c. eta increases. the risk. of cerebral. infarction 2007 39 2 212 217 - 229.
Functional snp in an sp1-binding site of agtrl1 gene is associated with susceptibility to brain infarction. Hum Mol GenetHata J. Matsuda K. Ninomiya T. Yonemoto K. Matsushita T. Ohnishi Y. Saito S. Kitazono T. Ibayashi S. Iida M. Kiyohara Y. Nakamura Y. Kubo M. 2007 16 6 630 639 - 230.
AtherosclerosisYamada Y. Fuku N. Tanaka M. Aoyagi Y. Sawabe M. Metoki N. Yoshida H. Satoh K. Kato K. Watanabe S. Nozawa Y. Hasegawa A. Kojima T. Identification of. as celsr a. susceptibility gene. for ischemic. stroke in. japanese individuals. by a. genome-wide association. study 2009 207 1 144 149