缺血性脑血管病患者趋化因子受体CX3CR1基因T280M多态性的研究

目的探讨缺血性脑血管病(ICVD)患者趋化因子受体CX3CR1基因T280M的多态性及其频率。方法采用聚合酶链反应和限制性片段长度多态性方法检测165例ICVD患者(脑梗死85例,腔隙性脑梗死40例,短暂性脑缺血发作40例)与150名健康对照者(正常对照组)CX3CR1基因T280M的多态性,比较两组及ICVD亚组的基因频率。结果正常对照组CX3CR1基因T280M只有TT和TM基因型,ICVD组有TT、TM和MM3种基因型,两组间基因型的差异有统计学意义(P<0.05);ICVD组M等位基因频率(8.7%)明显高于正常对照组(2.3%)(P<0.01);不同ICVD亚组之间基因型及M等位基因频率的差异无统计学意义(均P>0.05)。结论ICVD患者趋化因子受体CX3CR1基因T280M有MM基因型,并且M等位基因的频率明显增高,提示CX3CR1基因T280M多态性可能与ICVD有关。     

河南汉族人群eNOS基因VNTR多态性与缺血性脑血管病的关系

目的 探讨河南汉族人群内皮细胞性一氧化氮合酶(eNOS)基因内含子4可变性重复序列(VN-TR)的多态性与缺血性脑血管病(ICVD)的关系.方法 应用聚合酶链反应(PCR)技术,检测488例缺血性脑血管病患者的基因型,并与对照组比较.结果 缺血性脑血管病组eNOS基因ab基因型的频率(18.4%)明显高于对照组(13.57%),a等位基因的频率(11.5%)也明显高于对照组(7.7%),差异均有显著性(P＜0.05).结论 eNOS基因ab基因型与缺血性脑血管病有相关性,等位基因a可能是缺血性脑血管病的危险因素.     

胱硫醚β合酶基因T833C多态及血浆同型半胱氨酸水平与缺血性脑血管病的相关性

目的 探讨血浆同型半胱氨酸(Hcy)水平、胱硫醚β合酶(CBS)基因T833C多态与缺血性脑血管病(ICVD)的相关性.方法 应用高效液相色谱仪-FD法和扩增阻滞突变体系法(ARMS)检测360例ICVD患者和210名健康体检者的血浆Hcy水平和CBS T833C基因型,并进行相关分析.结果 ICVD组和对照组空腹血浆Hcy浓度分别为(17.6±4.8)μmol/L和(13.3±4.3)μmol/L,差异有统计学意义(t=10.716,P<0.05).ICVD组CBS基因第833位点T/T、T/C、C/C和基因型频率与对照组比较差异无统计学意义(χ2=o.785,P>0.05),C等位基因频率与对照组差异也无统计学意义(χ2=0.941,P>0.05).ICVD组各亚组CBS基因第833位点T/T和T/C+C/C基因型频率比较差异无统计学意义(χ2=1.691,P>0.05),C等位基因频率比较差异也无统计学意义(χ2=1.617,P>0.05).CBS T833C不同基因型之间血浆Hcy水平不同(F=6.56,P<0.05),TC、CC基因型组血浆Hcy水平明显高于TT基因型组,TC、CC基因型组间血浆Hcy水平差异无统计学意义.结论 血浆Hcy水平升高可能为ICVD的危险因素,CBS T833C基因多态可能不是ICVD的独立危险因子.     

磷酸二酯酶4D基因多态性与缺血性脑血管病的关系

目的 探讨中国汉族人群磷酸二酯酶4D (PDE4D) 基因多态性与缺血性脑血管病(ICVD)的关系.方法 采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测116例ICVD患者和110名正常对照者PDE4D基因SNP45、SNP83和rs918592位点的多态性及其与糖代谢指标的关系.结果 PDE4D基因rs918592的A等位基因频率ICVD组(58.6%)、腔隙性脑梗死亚组(63.8%)较正常对照组(48.6%)明显增高(均P<0.05);rs918592、SNP83基因型及等位基因频率各组间差异无统计学意义(均P>0.05);SNP45位点未见多态性.糖代谢指标在不同的SNP83、rs918592 基因型间差异无统计学意义(均P>0.05).结论 中国汉族人群PDE4D基因rs918592位点上A等位基因可能是ICVD的危险因素之一; PDE4D基因可能不是通过糖代谢影响ICVD的发生.     

磷酸二酯酶4D基因SNP83位点与新疆维吾尔族、汉族缺血性脑血管疾病的相关性

目的探讨新疆维吾尔族、汉族磷酸二酯酶4D基因(phosphodiesterase 4D,PDE4D)SNP83位点与缺血性脑血管疾病(ischemic cerebral vascular disease,ICVD)的关系。方法选取新疆地区缺血性脑血管疾病患者207例(维吾尔族109例,汉族98例)与正常对照组216例(维吾尔族110例,汉族106例),应用聚合酶链反应-限制性片段长度多态性技术检测PDE4D基因SNP83位点多态性,采用病例-对照的关联分析方法进行基因型和等位基因频率分布。结果新疆维、汉两民族PDE4D基因SNP83的基因型和等位基因频率在病例组与对照组间的分布差异有统计学意义(P<0.05);汉族病例组与对照组的基因型和等位基因分布频率差异有统计学意义(P<0.05)。男性病例组中PDE4D基因SNP83基因型分布频率和等位基因频率显著高于男性对照组(P<0.05),并发现携带C等位基因的个体发生缺血性脑血管疾病的危险性显著增加,其OR值为6.486(P<0.05)。结论新疆维吾尔族和汉族之间PDE4D基因SNP83多态性存在差异,并发现在汉族、男性人群中PDE4D基因SNP83多态性与缺血性脑卒中的发病风险存在关联。     

血管紧张素转换酶基因多态性与白族脑血管病患者的相关性研究

目的研究血管紧张素转换酶(ACE)基因插入/缺失多态性与云南大理白族脑血管病患者的相关性。方法应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,对73例白族脑血管病(ICVD)组患者(其中脑梗死40例,脑出血33例)和43例性别年龄相匹配的白族健康对照组进行ACE基因型检测和基因插入/缺失多态性分析;并进行ACE基因双向测序。结果(1)脑梗死组的DD基因型频率和D等位基因频率明显高于对照组(P<0.05);(2)脑出血组与对照组相比较,未发现DD基因型频率和D等位基因频率有明显差异(P>0.05);(3)脑血管组内伴高血压与不伴高血压,伴糖尿病与不伴糖尿病,伴血脂异常与血脂正常者相比较,未发现DD基因型频率和D等位基因频率有显著差异(P>0.05);(4)D等位基因和I等位基因其核苷酸序列和长度与国内外文献报道无明显差别。结论(1)ACE基因插入/缺失多态性与脑梗死的发生有关联性,DD基因型和D等位基因是脑梗死患者的高危因素;(2)ACE基因插入/缺失多态性与脑出血发生未发现有关联性;(3)脑血管病的其他相关危险因素如高血压,糖尿病,血脂与ACE基因多态性可能无关联;(4)ACE基因16内含子...     

云南白族、汉族人群载脂蛋白E基因多态与缺血性脑血管病的相关性

目前已知,缺血性脑血管病(ICVD)的主要发病原因为动脉粥样硬化,而大量研究表明,ApoE基因型是动脉粥样硬化在个体间发病差异的主要因素.中国云南省白、汉两民族ICVD患者ApoE基因的研究国内外还未见报道,我们采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术和基因测序法同时检测ApoE基因多态,旨在探讨云南白、汉两民族人群中ApoE基因与ICVD的关系.     

NOS3基因多态性与血脂、缺血性脑卒中的相关性研究

目的为了探索NOS3基因G894T多态性与缺血性脑卒中的关联,以及与血脂的关系。方法聚合酶链式反应-限制性片段长度多态性(PCR-RFLP),琼脂糖凝胶电泳检测100例缺血性脑卒中患者和对照组80例健康志愿者的NOS3基因G894T多态性。自动生化分析仪检测血脂指标。结果 (1)卒中组与对照组相比GT(27/100和22/120)和TT(7/100和2/120)基因型分布频率较高(P 0. 05)。T等位基因分布在卒中组(20. 5%)也显著高于对照组(10. 83%)(P 0. 01);(2)卒中组中TT基因型携带者血脂水平TC和LDL-C显著高于GG和GT基因型患者,而其他血脂水平无显著差异;(3)关联分析显示TT基因型与卒中患病风险具有相关性(P 0. 05)。结论 NOS3基因多态性与缺血性脑卒中发病存在关联,TT基因型携带者患病风险高于GG基因型携带者。     

SNaPshot微测序技术分析5-脂氧合酶激活蛋白基因与缺血性脑血管病的相关性

目的 探讨5-脂氧合酶激活蛋白(ALOX5AP)基因SG13S114A/T和SG13S32A/C两位点多态性与河南汉族人群缺血性脑血管病(ICVD)的遗传易患性.方法 采用SNaPshot多重微测序技术检测246例河南汉族ICVD患者和245名健康对照者ALOX5 AP基因SG13S114和SG13S32位点的多态性,运用SPSS16.0软件进行基因型频率、等位基因频率的比较,SHEsis软件进行单倍型分析和连锁不平衡检验.结果 ICVD组SG13S114位点AA基因型频率及A等位基因频率明显高于对照组,差异有统计学意义.经性别及年龄分层分析发现,男性ICVD患者及年龄小于50岁的ICVD患者SG13S114位点的AA基因频率及A等位基因频率亦明显高于对照组,差异有统计学意义.单倍型分析发现:ICVD组A-A单倍型频率(30.4％)显著高于对照组(23.5％),差异具有统计学意义(OR=1.419,95％ CI1.068～1.885,P=0.015);T-C单倍型频率(22.0％)显著低于对照组(28.8％),差异具有统计学意义(OR=0.698,95％ CI0.523 ～0.932,P=0.014).结论 SG13S114位点可能是河南地区汉族人群ICVD的遗传风险因子,并且该位点与男性ICVD患者及年龄小于50岁ICVD患者的发病关系更为密切.A-A单倍型可能是河南汉族人群ICVD发生的风险因子,T-C单倍型可能对河南汉族人群ICVD的发生具有保护作用.     

纤维蛋白原基因多态性与缺血性心脑血管病的相关性研究

目的探讨Aα纤维蛋白原58G/A基因多态性与血浆纤维蛋白原(Fg)水平、功能及与缺血性脑血管病的相关性。方法用PCRRFLPs技术检测54例缺血性心脑血管病患者和70例健康对照者的Aα58G/A基因多态性;采用血浆Fg功能自动检测系统测定血浆水平及功能。结果A等位基因频率在病例组为0.315,对照组为0.271,2组比较无显著性差异(P>0.05);病例组血浆Fg水平及功能显著高于对照组;病例组A等位基因携带者血浆Fg功能高于GG基因型组(P=0.038)。结论中国汉族人群存在A58G/A基因多态性;虽然缺血性心脑血管病患者不仅血浆Fg水平增高而且伴有Fg功能增强,但A等位基因不显著影响血浆Fg水平,与缺血性心脑血管病的发病无明显关系。     

Age-dependent association of apolipoprotein E genotypes with stroke subtypes in a Japanese rural population

BACKGROUND AND PURPOSE: The association between apolipoprotein E (apoE) polymorphisms and stroke has been controversial. These controversies may be due to inaccurate classification of stroke and differences in age ranges. We investigated the association between apoE genotypes and stroke subtypes (confirmed by CT or MRI findings) by case-control study in a Japanese rural population. METHODS: First-ever-stroke patients (n=322; cerebral infarction, n=201, intracerebral hemorrhage, n=84, and subarachnoid hemorrhage, n=37) aged 40 to 89 years were recruited from Hokuetsu Hospital, Japan. Healthy controls (n=1126) were selected from the general population in the same area. ApoE genotypes were determined by restriction fragment-length polymorphism analysis. RESULTS: Compared with apoE epsilon3/epsilon3 subjects, epsilon2 carriers had a 2-fold risk of cerebral infarction (OR 1.9, 95% CI 1.1 to 3.2). Among cerebral infarction patients, epsilon2 carriers had increased risks of cortical infarction (OR 2.4, 95% CI 1.3 to 4.6) (an anatomic subtype) and atherothrombosis (OR 3.9, 95% CI 1.7 to 9.0) and cardioembolism (OR 4.9, 95% CI 1.6 to 14.4) but not lacunar infarction (clinical subtypes). ApoE epsilon4 carriers had a 2. 5-fold risk of subarachnoid hemorrhage (OR 2.5, 95% CI 1.1 to 5.4). ApoE epsilon2/epsilon2 subjects had an increased risk of intracerebral hemorrhage (OR 4.4, 95% CI 1.0 to 19.7). ApoE epsilon3/epsilon4 subjects showed approximately 2-fold increased risk of atherothrombosis (OR 2.1, 95% CI 1.0 to 4.1) and intracerebral hemorrhage (OR 1.8, 95% CI 1.0 to 3.3). The association between epsilon2 and stroke was accentuated in subjects aged 70 years or older but not in those aged 40 to 69 years. CONCLUSIONS: Our study suggests that apoE epsilon2 is a risk factor for atherothrombosis, cardioembolism, and intracerebral hemorrhage, whereas epsilon4 is a risk factor for atherothrombosis, intracerebral hemorrhage, and subarachnoid hemorrhage. The occurrence of stroke may be affected by interaction between age and apoE gene polymorphisms.     

Association of a 27-bp repeat polymorphism in ecNOS gene with ischemic stroke in Chinese patients

OBJECTIVE: To investigate the association between a 27-bp repeat polymorphism of the ecNOS gene in 364 patients with ischemic stroke and 516 control subjects. BACKGROUND: The incidence of stroke in China is higher than that of coronary artery disease. Furthermore, ischemic stroke is more prevalent than hemorrhagic stroke. A 27-bp repeat polymorphism in intron 4 of the endothelial constitutive nitric oxide synthase (ecNOS) gene has been reported to associate with coronary artery disease in an Australian population, but no association was found between this polymorphism and ischemic stroke in a Japanese population. METHODS: All patients and unrelated control subjects were screened by CT. All participants lived in central China. Multivariate logistic regression analysis was used to determine the independent roles of this ecNOS gene polymorphism and covariates in ischemic stroke. RESULTS: These results indicated an association between the ecNOS a allele and ischemic stroke in the Chinese patients studied (7.8 versus 17.0%; OR = 2.44; 95% CI = 1.60 to 3.71, p < 0.0001). CONCLUSION: The ecNOS a allele in intron 4 may be an independent risk factor for ischemic stroke in the Chinese population studied, especially in those lacking other conventional risk factors.     

Apolipoprotein E polymorphism and central nervous system tumors: correlation with cell proliferation indices and clinical outcome

AIMS: This study was designed to determine whether the polymorphism of apolipoprotein E (apoE), one of the key regulatory proteins in cholesterol metabolism, is related to varying susceptibility to central nervous system (CNS) neoplasms, and to evaluate any possible interaction between this polymorphism and tumor cell proliferation or clinical outcome. METHODS AND RESULTS: 53 CNS tumors were selected. Follow-up and survival data were available for 36 patients. ApoE genotypes and cell proliferation indices (nucleolar organizer regions, MIB-1, PCNA, p53) were determined from paraffin-embedded tissue by standard methods. Each of the indices of cell proliferation correlated positively with tumor grade and negatively with duration of clinical follow-up and survival. There was a non-significant trend for apoE epsilon2 allele carriers to have high-grade tumors and apoE epsilon4 allele carriers to have low-grade tumors. Possession of apoE epsilon4 was associated with a more advanced age of disease presentation (p < 0.01) and a longer duration of follow-up (p < 0.04). No significant correlations were found between possession of either apoE epsilon2 or apoE epsilon4 alleles and indices of cell proliferation. CONCLUSIONS: These preliminary findings suggest that possession of apoE epsilon4 allele may correspond to a more favorable clinical course in terms of more advanced age of disease presentation, and longer duration of follow-up and survival in patients with CNS neoplasms.     

Cerebral hemorrhage and apoE

The ɛ4 allele of apolipoprotein E (apoE) is found more commonly among patients with Alzheimer’s disease (AD) than in the normal population. ApoE is associated with brain amyloid, a component of cerebral amyloid angiopathy (CAA), which is both a pathological feature of AD and a frequent cause of lobar intracerebral hemorrhage (ICH). We hypothesized that the frequency of ɛ4 allele is higher in patients with CAA-related ICH than in hypertensive ICH and in the normal population. To test this hypothesis we compared the frequency of apoE alleles in four populations: 24 patients with lobar ICH, 24 matched patients with hypertensive ICH, 24 matched normal controls, and 173 population controls. Although there was a tendency to a higher frequency of apoE ɛ4 in lobar ICH patients, we found no significant differences in the frequency of this allele between the four studied populations. In addition we did not confirm the finding of some authors of a higher frequency of apoE ɛ2 in patients with lobar ICH than in the normal population. Previous studies on the subject are discussed. The relationship between apoE polymorphism and lobar CAA-related ICH remains to be clearly defined. Received: 28 August 1998 Received in revised form: 19 February 1999 Accepted: 23 February 1999     

Effect of Genetic Polymorphism +294T/C in Peroxisome Proliferator-Activated Receptor Delta on the Risk of Ischemic Stroke in a Tunisian Population

PPARδ +294T/C polymorphism was investigated in diabetics, in normolipidemic healthy controls, in dyslipidemic and nondyslipidemic coronary artery disease patients but never in ischemic stroke patients. The aim of this study was to explore, for the first time, the relationship between the genetic polymorphism of PPARδ and the risk of ischemic stroke among patients with diabetes. The study group consisted of 196 patients with ischemic stroke and 192 controls. Plasma concentrations of total cholesterol, triglycerides, low-, and high-density lipoprotein did not differ significantly between subjects carrying the TT genotype and those carrying the CC/TC genotype in both ischemic stroke patients (with or without diabetes) and control groups. The +294C allele (CC + CT genotypes) as compared with TT genotypes was found to be higher in total ischemic stroke patients than in controls. On the other hand, no interaction between diabetes and PPAR +294T/C polymorphism on the risk of ischemic stroke was found (p?=?0.089). The PPARδ +294T/C polymorphism was associated with the risk of ischemic stroke in Tunisian subjects. This polymorphism has no influence on plasma lipoprotein concentrations and body mass index either in healthy subjects or in ischemic stroke patients with or without diabetes both in males and females.     

Transplantation of neural stem cells modulates apolipoprotein E expression in a rat model of stroke

The expression of apolipoprotein E (apoE) after ischemic brain damage has been associated with plasticity involved in promoting functional recovery. We therefore examined the expression and distribution of apoE in rats that received intraparenchymal grafts of the conditionally immortal stem cell line MHP36 either ipsilateral or contralateral to the lesion or intraventricular grafts 4 months after transplantation. ApoE immunoreactivity was highly expressed in the striatum, somatosensory cortex, and thalamus of the lesioned hemisphere in all rats subjected to middle cerebral artery occlusion. Only in rats with intraparenchymal grafts, apoE was significantly upregulated in the contralateral hemisphere, whereas levels and distribution in rats with intraventricular grafts resembled those of ischemic controls. In ischemic rats, apoE was seen in both astrocytes and neurons on the lesioned side, and in grafted rats, apoE was present in host and transplanted neurons and astrocytes. Previously we have shown that intraparenchymal grafts reduced sensorimotor asymmetry, whereas intraventricular grafts improved cognitive dysfunction, with transplanted cells being widely distributed in cortex, striatum, and corpus callosum on both sides of the brain in all grafted groups. Thus, stem cells grafted in the parenchyma are not only capable of limited expression of apoE in the host brain but also trigger a robust increase on the side contralateral to stroke damage where this does not normally occur. Findings that parenchymal, but not ventricular, grafts facilitated sensorimotor recovery suggests that apoE might contribute to plastic changes in relevant pathways, possibly on both sides of the brain. In contrast, no evidence was found for an association between apoE and recovery of cognitive function in rats with intraventricular grafts.     

Correlation between genetic polymorphisms and stroke recovery: analysis of the GAIN Americas and GAIN International Studies

Background and purpose: Recovery after stroke occurs on the basis of specific molecular events. Genetic polymorphisms associated with impaired neural repair or plasticity might reduce recovery from stroke and might also account for some of the intersubject variability in stroke recovery. This study hypothesized that the ApoE ε4 polymorphism and the val⁶⁶met polymorphism for brain‐derived neurotrophic factor (BDNF) are each associated with poorer outcome after stroke. Associations with mitochondrial genotype were also explored. Methods: Genotypes were determined in 255 stroke patients who also received behavioral evaluations in the Glycine Antagonist In Neuroprotection (GAIN) clinical trials. The primary outcome measure was recovery during the first month post‐stroke, as this is the time when neural repair is at a maximum and so when genetic influences might have their largest impact. Two secondary outcome measures at 3 months post‐stroke were also examined. Results: Genotype groups were similar acutely post‐stroke. Presence of the ApoE ε4 polymorphism was associated with significantly poorer recovery over the first month post‐stroke (P = 0.023) and with a lower proportion of subjects with minimal or no disability (modified Rankin score 0–1, P = 0.01) at 3 months post‐stroke. Indeed, those with this polymorphism were approximately half as likely to achieve minimal or no disability (18.2%) versus those with polymorphism absent (35.5%). Findings were confirmed in multivariate models. Results suggested possible effects from the val⁶⁶met BDNF polymorphism and from the R0 mitochondrial DNA haplotype. Conclusions: Genetic factors, particularly the ApoE ε4 polymorphism, might contribute to variability in outcomes after stroke.     

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.     

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.