ApoE和Slco1B1基因多态性与缺血性脑卒中的相关性分析

目的 探讨汉川市汉族人群ApoE基因和Slco1B基因多态性与缺血性脑卒中的相关性。方法 收集450例缺血性脑卒中患者(实验组)和健康对照人群(对照组)的血液,通过直接测序法分析对照组和实验组人群ApoE和Slco1B1基因型; Hardy-Weinberg平衡定律检测遗传平衡性。结果(1)ApoE基因型频率符合Hardy-Weinberg平衡定律(P=0.982),ApoE基因型可能与缺血性脑卒中有关(P=0.034);(2)Slco1B1基因型频率符合Hardy-Weinberg平衡定律(P=0.469),Slco1B1基因型可能与缺血性脑卒中有关(P=0.031)。结论 汉川市汉族人群ApoE基因和Slco1B1基因多态性可能与缺血性脑卒中有关。     

Polymorphism of apolipoprotein E (APOE) and lipoprotein lipase (LPL) genes and ischaemic stroke in individuals of Yakut ethnicity

There is evidence that most forms of ischaemic stroke (IS) result from synergistic effects of the modifiable predisposing factors and multiple genes. In the present work, we report results of case-control study of IS association with apolipoprotein E gene (APOE) (promoter and coding polymorphisms) and lipoprotein lipase gene (LPL) (presence/absence of a HindIII cutting site). We studied 107 unrelated patients of Yakut ethnicity (69 men and 38 women, mean age 58.4+/-11.5 years) with first-ever IS in carotid/middle cerebral artery regions. The control group included 101 subjects of the same ethnicity (61 men and 40 women, mean age 57.6+/-11.6 years) free of clinically detectable cerebrovascular disease, and without any history of stroke. A positive association of IS with APOE -427T allele (p=0.0012, OR=3.99) and -427T/T genotype (p=0.0005, OR=4.96) and a negative association with -427C allele (p=0.0012, OR=0.25), -427T/C genotype (p=0.0003, OR=0.18), epsilon2 allele (p=0.018, OR=0.35), epsilon2/3 genotype (p=0.017, OR=0.28) and -491A/-427C/epsilon2 haplotype (p=0.0026, OR=0.18) were observed. For atherothrombotic subgroup the same allele and genotype associations were found plus association with APOE -491A allele (p=0.026, OR=3.98). No reliable IS associations were found with LPL T+495G (HindIII) polymorphism. An association of APOE promoter polymorphisms (A-491T, T-427C) with an IS is shown in our study for the first time. Our study provides evidence for the role of APOE gene as a prognostic genetic marker for IS, especially for its atherothrombotic subtype.     

脂蛋白脂酶Ser447Stop基因多态与脑梗死的相关性

目的 探讨脂蛋白脂酶(LPL)Ser447Stop基因多态与脑梗死的相关性.方法 受试者共883人,其中脑梗死组563例[包括动脉粥样硬化(AS)性脑梗死329例和腔隙性脑梗死234例],对照组320名,应用聚合酶链反应一限制性片段长度多态性方法,对LPL基因Ser447Stop位点进行基因多态性检测.结果 脑梗死组、AS性脑梗死组和腔隙性脑梗死组LPL Ser447Stop GG+CG基因型频率与对照组相比,差异无统计学意义,AS性脑梗死组G变异等位基因频率(64例,9.7%)与对照组(42例,6.6%)相比差异有统计学意义(X2=3.99,P=0.045).相对于C等位基因,G等位基因的彻值为1.510(95%C/1.012～2.261).结论 LPL Ser447Stop G变异等位基因携带者患AS性脑梗死的危险高于非携带者.G变异等位基因可能是AS性脑梗死高危险性的遗传标志之一.     

Association of apolipoprotein E genotype and cerebrovascular disease risk factors in a Turkish population

The purpose of the present study was to investigate the predictive role of apolipoprotein E genotypes for stroke-related risk factors in the Turkish population. Among 100 stroke patients and 30 healthy subjects included in the study, most frequent Apo E genotype was epsilon3/3, compatible with polymorphic distribution of Asian population. VLDL and triglyceride levels in epsilon2/4(+) subjects were higher than in epsilon2/4(-) patients. HDL and homocysteine levels were higher in epsilon4/4 (+) subjects than in epsilon4/4 (-) stroke patients. These results suggest that ApoE polymorphism in this population was not associated with any other demographic or clinical variables except for lipid profiles and homocysteine levels.     

Association of C3435T multi drug resistance gene-1 polymorphism with aspirin resistance in ischemic stroke and its subtypes

Aspirin is the most commonly used antiplatelet drug for treatment of a serious vascular event, most notably myocardial infarction and stroke. Significant fraction of aspirin treated patients is resistant to the antiplatelet effects of the drugs. Previous studies have suggested that a genetic basis for aspirin resistance exists. Therefore the present study was taken up to investigate the role of C3435T polymorphism (rs 1045642) of multiple drug resistance-1 (MDR-1) gene with aspirin resistance in stroke patients. Five hundred and sixty ischemic stroke patients and 560 age and sex matched healthy controls were involved in the study. Baseline clinical data were collected and follow-up telephone interviews were conducted with patients at 3, 6 and 12 months post event to determine stroke outcome. Blood samples were collected and genotypes determined. Significant difference was observed in the genotype distribution and allele frequency between patients and controls. The results were confirmed by a step wise multiple logistic regression analysis controlling all other confounding risk factors [adjusted Odds ratio=3.132 (95% CI; 2.043-4.800; p<0.001)]. There was a significant difference in genotype distribution between drug responders and non-responders. The risk of aspirin resistance was significantly high in patients with TT genotype in comparison to those with CC genotype [(TT vs. CC, χ(2)=6.268; p=0.012, Odds ratio=1.85) (95% CI; 1.142-3.017) (adjusted Odds ratio=2.465; 95% CI; 1.895-4.625 and p<0.001)]. As far as the stroke subtypes are concerned TT genotype associated significantly with aspirin resistance in intracranial large artery atherosclerosis. Our results indicate that the risk of aspirin resistance is more in patients with 3435TT genotype than in those with CC genotype. However, this is a preliminary study and a large study of replication is needed to confirm our results.     

Association of acute ischemic stroke with the MTHFR C677T polymorphism but not with NOS3 gene polymorphisms in a Singapore population

Background and purpose: The association of polymorphisms in the nitric oxide synthase 3 (NOS3) gene (T‐786C, variable number tandem repeats 4A/B/C, and G894T) and in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) with acute ischemic stroke have been reported. Methods: First‐time onset acute ischemic stroke patients (n = 120) and controls (n = 207) with no past history of stroke were compared. Allele specific gene amplification and restriction fragment length polymorphism (RFLP) analysis were used to determine the genotype and allelic frequencies in both groups. Plasma homocysteine (Hcy) and nitrite levels were measured. Results: No significant association of NOS3 polymorphisms with ischemic stroke was noted. The TT genotype of the MTHFR C677T polymorphism was significantly associated with ischemic stroke (P = 0.004). Elevated plasma Hcy levels were also significantly associated with ischemic stroke (P = 0.001). Conclusions: The TT genotype of C677T polymorphism in the MTHFR gene contributes to genetic susceptibility of acute ischemic stroke in a Singapore population.     

The -174G/C polymorphism of the interleukin 6 gene is a hallmark of lacunar stroke and not other ischemic stroke phenotypes

BACKGROUND AND PURPOSE: The CC genotype of the -174 G/C interleukin (IL)-6 polymorphism has been associated with lacunar stroke. However, it remains unsettled whether this polymorphism is also associated with other ischemic stroke phenotypes. METHODS: The -174 G/C IL-6 polymorphism was genotyped in patients with lacunar stroke (n = 89), stroke due to large vessel disease (n = 82), cardioembolism (n = 53), stroke of undetermined cause (n = 49) and in white controls without any history of stroke (n = 105) by PCR and restriction enzyme analysis. Independent predictors of the -174 G/C IL-6 genotypes were assessed using multivariate logistic regression models adjusted for demographics, risk factors and disease state. RESULTS: The prevalence of the CC genotype was 8.5% in large vessel disease, 7.5% in embolism, 19.1% in lacunar stroke, 14.3% in stroke of undetermined cause and 8.6% in controls. The CC genotype was independently associated with lacunar stroke only (adjusted OR 3.22, 95% CI 9.09-1.12). Contrarily, there were no significant differences in genotype and allele distribution in the remainder of ischemic stroke phenotypes. Pooling of patients with nonlacunar stroke did not show any independent association with the CC genotype as compared with controls (OR 1.01, 95% CI 2.77-0.36). CONCLUSIONS: The unique association between the CC genotype of the -174 G/C IL-6 polymorphism and lacunar stroke suggests a particular susceptibility of small deep penetrators of cerebral arteries to IL-6-mediated inflammatory damage.     

ACE I/D polymorphism in Korean patients with ischemic stroke and silent brain infarction

Objectives –  Angiotensin-converting enzyme ( ACE ) polymorphism may play a role in stroke and silent brain infarction (SBI) susceptibility, but the results among the populations studied to date have not been consistent. Thus, we investigated the association between ACE genotypes and ischemic stroke and SBI in Korean patients.
Subjects and methods –  DNA samples from 237 stroke patients, 264 SBI patients and 234 age-matched controls were amplified using polymerase chain reaction to detect the ACE ins/del (I/D) polymorphism. Genotype was determined by the presence of a 490-bp band ( I allele) or a 190-bp band ( D allele) in agarose gel electrophoresis.
Results –  Odds ratios of the I/D and D/D genotypes and the overall (I/D + D/D) for the I/I genotype were significantly different between stroke patients and normal controls. However, there was no significant difference between patients with SBI and controls.
Conclusions –  This study is the first report of a significant association between ACE polymorphism and ischemic stroke in the Asian population. Although no consistent associations have been found between ACE polymorphism and stroke in the populations studied to date, the ACE polymorphism may be a genetic determinant of ischemic stroke, at least in Korean patients.     

HDL-Cholesterol, total cholesterol, and the risk of stroke in middle-aged British men

BACKGROUND AND PURPOSE: The purpose of this study was to examine the relation between serum HDL cholesterol and total cholesterol and risk of stroke. METHODS: We carried out a prospective study in 7735 men, 40 to 59 years of age, drawn from 1 group practice in each of 24 British towns. Men with history of stroke were excluded (n=52). RESULTS: During the mean follow-up period of 16.8 years, there were 343 stroke cases (fatal and nonfatal) in the 7683 men with no history of stroke. Higher levels of HDL cholesterol were associated with a significant decrease in risk of stroke even after adjustment for potential confounders (top fifth versus lowest fifth: adjusted relative risk=0.68, 95% CI 0.46 to 0.99). The inverse relation was seen only for nonfatal strokes (adjusted relative risk=0.59, 95% CI 0.39 to 0.90; top fifth versus lowest fifth). Total cholesterol showed no graded association with fatal strokes, but men with levels > or =8.1 mmol/L (top 5% of the distribution) showed increased risk of nonfatal stroke, although this was not statistically significant after adjustment (adjusted RR=1.46, 95% CI 0.91 to 2.32). The beneficial effects of elevated HDL cholesterol on nonfatal stroke were seen in both smokers and nonsmokers and were more evident in men with hypertension than in normotensives. In hypertensive men, elevated HDL cholesterol (top fifth) was associated with a significant 50% reduction in risk of nonfatal strokes compared with men in the lowest fifth. CONCLUSIONS: Higher levels of HDL cholesterol were associated with a significant decrease in risk of nonfatal stroke. In contrast, elevated total cholesterol showed a weak positive association with nonfatal strokes. The marked inverse association between HDL cholesterol and stroke seen in hypertensives emphasizes the importance of those modifiable risk factors for stroke known to lower the concentrations of HDL cholesterol.     

MMP-2、MMP-9基因多态性与缺血性脑卒中临床分型及预后

目的探讨基质金属蛋白酶2(Matrix Metalloproteinase-2,MMP-2)基因C1306T、C735T和MMP-9基因C1562T多态性位点与缺血性脑卒中的关系。方法采用限制性片段长度多态性分析技术,检测缺血性脑卒中组232例和健康对照组235例MMP-2基因C1306T、C735T和MMP-9基因C1562T多态的分布。结果缺血性脑卒中组和对照组MMP-2 C1306T基因型和等位基因频率分布无统计学意义。在动脉粥样硬化性血栓性脑梗死组MMP-9 C1562T的CT+TT基因型频率和T等位基因频率、MMP-2 C735T的CC基因型频率和C等位基因频率明显高于对照组(P<0.05),而在脑栓塞组、腔梗组差异无统计学意义(P>0.05)。多因素Logistic回归分析,MMP-2、MMP-9不同基因型别与缺血性脑卒中预后无显著相关性(P>0.05)。结论 MMP-2 C735T的C等位基因、MMP-9 C1562T的T等位基因是动脉粥样硬化性血栓性脑梗死的遗传易感基因之一。MMP-2、MMP-9基因多态性与缺血性脑卒中预后无关。     

Evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of ischaemic stroke.

Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with increased incidence of stroke in some populations, although contradictory results have been reported. The aim of this study was to determine the allelic frequency and the genotypic distribution for ACE gene polymorphism in Turkish patients with ischemic stroke compared to appropriate healthy controls and to correlate the genetic findings with stoke type. One hundred and eight patients with ischemic stroke versus 79 healthy controls were studied for the presence of ACE gene polymorphism detected by PCR. Genotypes were defined as DD, II and ID according to the presence of the D (deletion) and I (insertion) alleles. There was no statistically significant difference in either the genotypic distribution or allelic frequency between the patients versus healthy controls (chi2 = 0.105; df = 1; p = 0.430). There was also no significant difference for ACE genotype distribution and allelic frequency within the stroke group classified according to Bamford criteria (chi2 = 4.827; df = 3; p = 0.185). Our data supports lack of association between DD genotype and/or D allele and ischemic stroke or subtypes of ischaemic stroke in the Turkish population.     

Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: a meta-analysis

Introduction

Previous studies suggested lipoprotein lipase (LPL) Ser447Ter and Asn291Ser polymorphisms were associated with the risk of ischemic heart disease, however, their effects on ischemic stroke were controversial. A meta-analysis was performed to assess the associations between these two LPL polymorphisms and the risk of ischemic stroke.

Methods

The electronic databases PubMed and Embase were used to identify relevant studies by two interviews independently. The pooled odds ratios (ORs) and weighted mean differences (WMD) with 95% confidence interval (CI) were estimated for the risk of ischemic stroke and the plasma lipids in various Ser447Ter genotypes respectively. A fixed or random effect model was selected for pooling data based on homogeneity test.

Results

13 studies including 4,681 ischemic stroke cases and 8,516 controls were involved in this meta-analysis. Overall, LPL Ter447 variant was associated with a significantly reduced risk for ischemic stroke (OR = 0.79, 95% CI: 0.68-0.93) both in Caucasian (OR = 0.87, 95% CI: 0.77-0.97) and East-Asian (OR = 0.65, 95% CI: 0.43-0.99), whereas no significant association of Ser291 variant was observed (OR = 1.25, 95% CI: 0.96-1.63). The Ser447Ter polymorphism may be more important in association with the decreased risk of atherosclerotic stroke (OR = 0.44, 95% CI: 0.32-0.62) which derived from significantly increased high density lipoprotein cholesterol, decreased triglyceride and total cholesterol in Ter447 carriers compared with non-carriers.

Conclusions

This meta-analysis indicated that LPL Ser447Ter polymorphism was associated with a significant reduction in the risk of ischemic stroke, especially atherosclerotic stroke subtype in both Caucasian and East-Asian.     

缺血性脑卒中与血脂水平关系的初步分析

目的研究血脂异常与缺血性脑卒中及其各亚型的关系。方法收集516例缺血性脑卒中患者及131例非缺血性卒中对照组个体的血脂情况,包括血总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）等指标,对其进行统计分析比较。并将其中131例缺血性脑卒中患者根据TOAST分型标准进行分型,将各亚组的血脂水平与对照组再进行比较。结果缺血性脑卒中组的HDL水平明显低于对照组,TC／HDL比值明显高于较对照组。其余血脂成分,包括TC、TG、LDL则未发现存在显著差异。亚组比较中,大动脉粥样硬化性卒中（LAA）组、心源性脑栓塞（CE）组、小动脉闭塞性卒中或腔隙性卒中（SAO）组的HDL水平明显低干对照组,而他们的TC／HDL比值则明显高于对照。其余血脂成分比较未见统计学差异。其他原因卒中（SOE）及不明原因卒中（SUE）均显示与血脂各成分无相关性。结论HDL在缺血性脑卒中患者明显降低,其保护因素降低可能是卒中发生的原因之一。TC／HDL比值可作为衡量血脂异常与缺血性卒中关系的指标之一。需要进一步进行基于卒中分型基础上的更大样本量的研究。     

NADPH氧化酶p22~(phox)亚基基因多态性与急性动脉硬化性脑梗死的关联性研究

目的探讨CYBA基因的多态性位点与急性动脉硬化性脑梗死的相关性。方法收集284例脑梗死患者(脑梗死组)及335例同期健康体检者(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测CYBA基因rs4673和rs3180279位点的基因型。结果 rs4673位点的基因型及等位基因频率分布在脑梗死组和对照组中差异无统计学意义(P0.05)。脑卒中组男性患者rs3180279位点GC、GG基因型的频率低于对照组,CC基因型的频率高于对照组(P=0.034)。结论 CYBA基因的rs4673位点与中国北方汉族人群的急性动脉硬化性脑梗死无相关性,男性rs3180279位点GG+GC基因型的携带者较CC基因型携带者动脉硬化性脑梗死的发病率可能更低。     

The (-174) G/C polymorphism in the interleukin-6 gene is associated with the severity of acute cerebrovascular events

BACKGROUND AND PURPOSE: Elevated plasma levels of interleukin-6 (IL-6) are associated with an increased risk and worse outcome of acute vascular events. A common G/C promoter polymorphism at nt (-174) of the IL-6 gene has been shown to affect basal IL-6 levels. Consequently, the IL-6 genotype may be associated with risk and outcome of ischemic stroke (IS). We investigated the statistical association between this polymorphism and cerebrovascular events, as well as the clinical outcome in patients with symptoms before the age of 60. METHODS: We examined 214 patients of 60 years or less with acute ischemic stroke or transient ischemic attack (TIA) and 214 age- and sex-matched healthy control subjects for the (-174) IL-6 G/C polymorphism by mutagenic separated polymerase chain reaction (MS PCR). Clinical severity of the vascular event was evaluated by validated scales at predefined points of time. RESULTS: In the total group of patients, the genotype and allele frequencies in the patient group (38% GG, 45% GC, 17% CC; allelic frequency: 60% G, 40% C) did not differ significantly from the control group. However, individuals homozygous for the (-174)G variant had significantly worse scores on the NIH Stroke Scale (NIHSS) already on admission and 1 week after the event. Also, patients with severe disability 1 week and 3 months after the event (Rankin Scale (RS) 4 or 5; NIH Stroke Scale> or =6) were significantly more often carriers of the GG genotype. In a multivariate analysis, the IL-6 (-174)GG genotype was significantly associated with severe disability after 1 week (RS 4-5; odds ratio (OR)=3.2, 95% CI: 1.5-6.6; p=0.002; NIHSS> or =6; OR=4.2, 95% CI: 1.6-11.1). CONCLUSIONS: The (-174)GG-genotype of the IL-6 gene is associated with severe stroke in young patients with acute cerebrovascular events. Further studies with larger patient groups are warranted to confirm these findings.     

Relationship between DRD4 polymorphism and lipid metabolism: what is the role of novelty seeking?

OBJECTIVE: This study examined the association of the dopamine receptor D4 (DRD4) gene polymorphism with the temperament dimension of novelty seeking (NS) on cardiovascular heart disease risk factors [the levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides]. METHOD: From the ongoing population-based study of 'Cardiovascular Risk in Young Finns', 125 participants were DRD4 genotyped in 1997 and responded to the NS scale of the Temperament and Character Inventory in 2001. Their cholesterol and triglyceride concentrations were assessed in 2001. RESULTS: Having a 2- or 5-allele DRD4 polymorphism was related to high HDL cholesterol levels in men, but to low HDL cholesterol levels in women. NS was related to triglycerides in men and to LDL in women, but this was mediated by behavioral, age, and weight factors, and NS was not the underlying factor for the association between the polymorphism and lipids. CONCLUSION: Our preliminary findings suggest that there is a link between the dopaminergic receptor gene DRD4 and lipid metabolism, but this link is dependent on gender.     

Polymorphisms at the osteoprotegerin and interleukin-6 genes in relation to first-ever stroke

BACKGROUND: Arterial calcification and osteoporosis often coexist, especially in postmenopausal women. Osteoporosis associates with a substantially increased risk of stroke in elderly women, suggesting that impaired estrogen signaling may link stroke and osteoporosis. Osteoprotegerin (OPG, TNFRSF11B) and interleukin-6 (IL-6, IL6) are putative target genes for estrogen signaling and have been implicated in both cardiovascular diseases and osteoporosis. We hypothesized that specific polymorphisms in these genes may be associated with increased risk of ischemic stroke or intracerebral hemorrhage (ICH). METHODS: We performed a population-based prospective nested case-control study, in which the relationships between polymorphisms (OPG-1181G/C, OPG-950T/C and IL6-174G/C) and ischemic stroke and ICH were examined. Definitive first-ever stroke events (n = 388), i.e. ischemic stroke (n = 320), ICH (n = 61) and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex and geographical region were studied. Univariate and multivariate models using conditional logistic regression, which included traditional risk factors, were used to test for association. RESULTS: Carriers of the OPG-1181C/C genotype had a significantly (p = 0.018) increased risk of ICH (OR, 2.69; 95% CI, 1.19-6.12) in the univariate analysis. After adjustments (hypertension, diabetes, BMI and triglycerides), this genotype remained significantly (p = 0.005) associated with ICH (OR, 6.04; 95% CI, 1.71-21.29). By contrast, no correlations were found between this genotype and ischemic stroke, nor between the OPG-950T/C or IL6-174G/C polymorphisms and stroke subtypes. CONCLUSIONS: In this population, the OPG-1181C/C genotype associates with first-ever ICH, implying that alterations in OPG-mediated signaling in the vasculature may be involved in the pathophysiology of this disease.     

Homocysteine,MTHFR 677C-->T polymorphism,and risk of ischemic stroke: results of a meta-analysis

BACKGROUND: Data are conflicting concerning risk for ischemic stroke associated with hyperhomocyst(e)inemia (hyper-Hcy) and a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T), which predisposes to hyper-Hcy in vivo. METHODS: Search of MEDLINE, Science Citation Index, and abstracts of conference proceedings revealed relevant articles. Exposure was defined as follows: 1) prevalence of hyper-Hcy; 2) absolute difference in the mean Hcy concentration between subjects with and without ischemic stroke; and 3) the MTHFR TT genotype frequency. Outcome was defined as ischemic stroke with or without neuroimaging. Inclusion criteria were retrospective and prospective studies with reported odds ratios (OR) or hazard ratios (HR) or arithmetic mean Hcy levels. Exclusion criteria were absence of OR or HR, outcome defined as carotid atherosclerosis or intima-media thickening, stroke in patients younger than 18 years old, and studies in languages other than English. Statistical analyses for between-study heterogeneity and pooled risk estimates were performed using Stata software (Stata Corporation, College Station, TX). RESULTS: Among 16 studies (1,487 stroke and 2,554 nonstroke cases), the pooled mean Hcy level in patients with ischemic stoke was 2.32 micromol/L (95% CI, 1.6 to 3.04; p < 0.001) greater than that in those without ischemic stroke. Among 14 included studies (1,769 stroke and 7,400 nonstroke cases), the pooled OR estimate of ischemic stroke associated with hyper-Hcy was 1.79 (95% CI, 1.61 to 2.0; p < 0.001). Among 19 included studies (2,788 stroke and 3,962 nonstroke cases), the OR associated with the TT genotype was 1.23 (95% CI, 0.96 to 1.58; p = 0.1). CONCLUSION: These data support an association between mild-to-moderate hyper-Hcy and ischemic stoke. The MTHFR TT genotype may have a small influence in determining susceptibility to ischemic stoke.     

Apolipoprotein A5 gene promoter region T-1131C polymorphism associates with elevated circulating triglyceride levels and confers susceptibility for development of ischemic stroke

The possible pathogenic role of triglycerides (TG) in the development of ischemic stroke is still under extensive investigation. Recently, apolipoprotein (apo)A5 gene promoter region T-1131C polymorphism has been shown to associate with elevated serum TG levels. In the current work, a total of 302 subjects were classified as being large vessel-associated, small vessel-associated, or belonging to a mixed group of ischemic stroke-affected patients. The level of TG was increased in all groups (p<0.01). The apoA5-1131C allele frequency was approximately twofold in all groups of stroke patients compared with the controls (5 vs 10–12%; p<0.05); and the apoA5-1131C allele itself was also found to associate with increased TG levels in all groups. In a multivariate logistic regression analysis model adjusted for differences in age, gender, serum cholesterol, hypertension, pressence of diabetes mellitus, smoking and drinking habits, and ischemic heart disease, a significantly increased risk of developing stroke disease was found in patients carrying the apoA5-1131C allele (p<0.05; odds ratio OR=2.1 [1.3–4.7]); this association was also proven for all subtypes of the stroke. The results presented here suggest that the apoA5-1131C allele is an independent risk factor for the development of stroke. Being that apoA5 gene is under the control of the peroxisome proliferator-activated receptor α, theoretically, the current observations also can have long-term therapeutic consequences.     

The Sma I Polymorphism in the von Willebrand Factor Gene Associated with Acute Ischemic Stroke

The von Willebrand factor (vWF) is a highly multimerized glycoprotein that promotes platelet adhesion and aggregation at a high shear rate, and also acts as a carrier of coagulation factor VIII. vWF has been identified as a risk factor for recurrent myocardial infarction in the general population. It has been reported that two polymorphisms of vWF gene promoter and the Thr789Ala polymorphism in vWF gene are associated with arterial thrombosis. The Sma I polymorphism is located in intron 2 of vWF gene. The relevance of this polymorphism to thrombotic disease was investigated by genotypic identification in two case–control studies: 107 patients with acute ischemic stroke, 49 patients with acute myocardial infarction (AMI), and 113 health controls age- and race-matched for each patient. Twenty-eight (26.2%) of the 107 patients with acute ischemic stroke, 8 (16.3%) of 49 patients with AMI, and 11 (9.7%) of 113 controls were found to be homozygous for CC genotype, respectively. The prevalence of the CC genotype in acute ischemic stroke was significantly higher than that of the normal controls (odds ratio [OR]=3.29, 95% confidence interval [CI]=1.54–7.01, .01>P>.001). However, the prevalence of the CC genotype in AMI was not significantly different from that of the normal controls (OR=1.81, 95% CI=0.68–4.82, .30>P>.20). Plasma vWF:Ag was also determined by enzyme-linked immunosorbent assay (ELISA) on the frozen plasma of 122 subjects. The mean plasma vWF:Ag levels of the controls, patients with acute ischemic stroke, and AMI were 0.468, 0.584, and 0.783 U/ml, respectively. The mean level of plasma vWF:Ag did not differ significantly between controls and patients with acute ischemic stroke (P=.195), but had significantly difference between controls and patients with AMI (P=.001). No association was found between the Sma I polymorphism and vWF plasma levels in controls, patients with acute ischemic stroke, or the AMI group (one-way ANOVA, P=.323, P=.315, P=.96). Results show that the Sma I polymorphism is strongly associated with increased risk of acute ischemic stroke, however, no association was observed between this polymorphism and AMI. This polymorphism of vWF may represent a newly identified risk factor for acute ischemic stroke in Chinese. Whether it is the real functional variant associated with acute ischemic stroke remains to be elucidated.