内皮源性一氧化氮合酶基因多态性与缺血性脑卒中相关性研究

目的通过病例对照研究,探讨内皮源性一氧化氮合酶(eNOS)基因多态性与缺血性脑卒中的关系。方法采用聚合酶链反应(PCR)和限制性片断长度多态性(RFLP)技术,对452例缺血性脑卒中患者和153例健康对照人群的eNOS基因rs3918181位点进行基因多态性检测。结果大动脉粥样硬化型脑梗死组的基因型与等位基因频率与正常对照组比较P>0.05,无统计学意义。腔隙性脑梗死组eNOS基因AA AG基因型频率明显高于对照组,相对于GG基因型,暴露于AA AG基因型人群的OR值为1.644(95%CI 1.124～2.405)。腔隙性脑梗死A等位基因频率也显著高于对照组,相对于G等位基因,A等位基因OR值为1.419(95%CI 1.061～1.898)。结论内皮源性一氧化氮合酶(e-NOS)基因rs3918181位点多态性与腔隙性脑梗死相关;A等位基因可能增加中国汉族人罹患腔隙性脑梗死的风险。     

内皮细胞性一氧化氮合酶基因可变性重复序列多态性与脑梗死的关系

目的　探讨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 (VNTR)的多态性与脑梗死 (CI)的关系。方法　应用聚合酶链反应 (PCR)技术 ,检测 15 2例CI患者的基因型 ,并与对照组比较。应用多元回归分析进行风险因素独立性分析。结果　CI组eNOS基因ab基因型的频率 (2 2 .36 % )明显高于对照组 (12 .2 8% ) ,a等位基因的频率 (12 .5 % )也明显高于对照组 (7.0 % ) ,差异均有显著性 (均P <0 0 5 )。ab基因型较bb基因型对CI的OR为 2 .0 5 (P <0 0 5 ) ,在用多元回归分析校正其他危险因素后OR为 1.98(P <0 0 5 ) ;CI组患者患高血压、高血脂、糖尿病及吸烟的比例较对照组为高 (均P <0 0 1) ,CI组患者年龄也较对照组高 (P <0 0 5 )。结论　eNOS基因ab基因型与CI有相关性 ,等位基因a可能是CI的独立危险因素。     

一氧化氮合酶家族及其基因多态性与缺血性脑卒中

脑卒中是一种多因素的复杂疾病,其遗传机制尚不完全明确。脑卒中又分为缺血性脑卒中和出血性脑卒中,其中缺血性脑卒中(ischemic stroke,IS)约占脑卒中的80%,是致残率和致死率最高的疾病之一。流行病学研究证实,脑卒中的发生与多个环境因素相关,其中吸烟、血脂异常、糖尿病、     

内皮型一氧化氮合酶与缺血性脑卒中

缺血性脑血管病一向在国内外具有很高的致残率和病死率,随着对其研究的深入,其治疗方向逐渐分为改善缺血区域供血及保护缺血神经细胞两方面,其中血管内皮细胞产生的一氧化氮(NO)是一项重要的内在脑血流调节剂及保护剂.本文综述了内皮型一氧化氮合酶(eNOS)对于缺血性脑卒中保护及治疗意义.     

中国人群中一氧化氮合酶Ⅲ基因多态性与阿尔茨海默病的关联性研究

目的:研究中国人群中一氧化氮合酶Ⅲ(NOS-Ⅲ)298G/T多态性与阿尔茨海默病(Alzheimerdisease,AD)发病的相关性;方法:通过实时定量荧光PCR和GeneAmp5700SDS软件检测530例AD患者和601例非痴呆对照者NOS-Ⅲ298G/T的基因多态性,并应用Logistic回归模型分析其与AD发病的相关性;结果:NOS-Ⅲ的G/G、G/T和T/T在AD组和对照组中分布差异无统计学意义(P>0.05),没有发现NOS-Ⅲ298G/T基因多态性与AD发病存在关联性;调整年龄和性别的影响后,G/G基因型并不是AD发病的危险因素,其OR值分别为1.17,P=0.73。结论:在中国人群中NOS-Ⅲ298G/T基因多态性与AD的发病不存在关联性。     

卡托普利上调缺血性脑卒中患者血小板一氧化氮合酶的实验和临床研究

目的　研究卡托普利对缺血性脑卒中患者血小板一氧化氮合酶 (NOS)的上调及临床应用。方法　测定急性缺血性脑卒中患者及健康体检者的血小板NOS及在体外加氧化低密度脂蛋白 (oxLDL)、卡托普利后血小板NOS的活性 ;检测患者服卡托普利前、服后 1个月及 3个月的血浆oxLDL、NOS、一氧化氮 (NO) ,血小板NOS、NO ,同时检查神经功能。结果　 (1)卒中组和对照组血小板加oxLDL后 ,NOS值均明显下降 (P <0 .0 1) ,卒中组下降更明显 ;(2 )两组血小板同时加卡托普利、oxLDL后 ,NOS值均明显升高 (P <0 .0 1) ,卒中组升高更明显 ;(3)两组血小板单纯加卡托普利后 ,其NOS值均明显升高 (P <0 .0 1) ,同样亦是卒中组升高更明显 ;(4 ) 4 0例缺血性脑卒中患者服用卡托普利后血浆oxLDL明显下降 ,血小板NOS、NO ,血浆NOS、NO明显增高 ,神经功能明显改善。结论　卡托普利有直接上调血小板NOS的作用 ,卡托普利通过提高血小板NOS活性的作用 ,可以改善内皮功能 ,防治脑卒中     

内皮一氧化氮合酶基因G894T多态性与动脉瘤性蛛网膜下腔出血的相关性研究

目的 研究eNOS基因第7外显子G894T多态性与动脉瘤性蛛网膜下腔出血(aSAH)的相关性.方法 利用聚合酶链反应(PCR)、琼脂糖凝胶电泳验证PCR反应产物,限制性片段长度多态性(RFLP)分析比较aSAH患者和对照者eNOS基因型的构成及等位基因频率的分布.结果 aSAH患者组的GT+TT基因型和T等位基因频率显著高于对照组,差异具有统计学意义.基因型分布在破裂的颅内动脉瘤直径大小之间差异无统计学意义,但是与aSAH患者预后相关.结论 eNOS基因G894T多态性可能是asAH发病的危险因子之一,GT+TT基因型与不良预后密切相关.     

神经肽Y基因启动子多态性与缺血性脑卒中的相关性研究

目的：探讨神经肽Y（NPY）基因启动子多态性与缺血性脑卒中的相关性。方法：采用聚合酶链反应（PCR）及基因测序技术,对450例缺血性脑卒中患者及423名正常对照者NPY基因启动子-399T／C（rs16147）基因型及等位基因频率进行检测。Logistic回归分析去除混杂因素影响,分析其与缺血性脑卒中发病的相关性。结果：脑卒中组NPY基因型和等位基因频率与正常对照组比差异有显著统计学意义,特别是在小动脉闭塞性脑卒中类型中。-399C等位基因与缺血性脑卒中存在相关性,是其重要危险因素（OR=2．398,95％CI=1．036-5．553,P=0．041）。结论：NPY基因启动子多态性可能与缺血性脑卒中的发病存在相关,具有-399C等位基因的个体发生缺血性脑卒中的风险可能显著增加。     

神经元型一氧化氮合酶基因多态性与脑梗死的相关性

目的探讨神经元型一氧化氮合酶(NOS1)基因多态性与脑梗死发病的关系。方法以rs9658281和rs2682820位点为遗传标记,采用聚合酶链式反应(PCR)和限制性片断长度多态性(RFLP)技术检测605例脑梗死患者和313例对照组人群的基因型。结果Rs9658281位点G等位基因频率较对照组明显增高(χ2=3.906,P=0.048,OR=1.362,95%CI1.003～1.850),这种差异在女性明显(χ2=6.689,P=0.010,OR=1.913,95%CI1.170～3.167)。Rs9658281位点的GG基因型频率较对照组明显增高(χ2=5.322,P=0.021,OR=1.473,95%CI1.060～2.047),这种差异在女性明显(χ2=9.299,P=0.002,OR=2.315,95%CI1.349～3.972)。经过多因素回归分析调整了传统危险因素的影响后,两组间仍有显著性差异(P=0.023)。Rs2682820位点的基因型频率和等位基因频率在脑梗死组和对照组的分布无显著差异(P>0.05)。结论神经元型一氧化氮合酶(NOS1)基因rs9658281位点多态性与脑梗死的发病可...     

诱导型一氧化氮合酶在被动吸烟女性缺血性脑卒中发病中的作用

目的探讨诱导型一氧化氮合酶(iNOS)在被动吸烟女性缺血性脑卒中发病中的作用。方法有被动吸烟史的女性缺血性脑卒中患者(被动吸烟组)100例,根据其被动吸烟指数分为指数<300亚组、300~599亚组、600~900亚组及>900亚组,每亚组25例。检测各亚组血清iNOS水平及颈动脉粥样硬化情况;并与无吸烟及被动吸烟史的健康女性(正常对照组)进行比较。结果不同被动吸烟指数亚组患者的血清iNOS水平、颈动脉内中膜厚度(IMT)及斑块检出率明显高于正常对照组(均P<0.01);被动吸烟指数与血清iNOS含量呈正相关(r=0.81,P<0.01);血清iNOS含量与IMT及斑块检出率呈正相关(r=0.69,r=0.72,均P<0.01)。结论长期被动吸烟的女性血清iNOS过度表达,可能促进了动脉粥样硬化的形成及缺血性脑卒中的发生。     

Association between Endothelial nitric oxide synthase G894T gene polymorphism and risk of ischemic stroke in North Indian population: a case-control study

Background and purpose: Stroke is a multi-factorial disease influenced by both genetic and environmental factors. The aim of this case-control study was to determine the association between Endothelial Nitric Oxide Synthase G894T (rs1799983) gene polymorphism and susceptibility to ischemic stroke (IS) in North Indian population.

Methods: In this present case-control study, genotyping was performed by using Polymerase chain reaction – Restriction fragment length polymorphism (PCR-RFLP) method for 250 IS patients and 250 age and sex matched controls. PCR results were confirmed by DNA sequencing. Frequency distribution of genotypes and alleles were compared between cases and controls using conditional logistic regression.

Results: Hypertension, Diabetes, Dyslipidemia, Low Socioeconomic Status and Family History of Stroke were found to be independent risk factors for IS. Mean age of cases and controls were 52.83 ± 12.59 and 50.97 ± 12.70 years. Multivariate logistic regression analysis showed a significant association between eNOS G894T (rs1799983) polymorphism and risk of IS [OR = 1.57; 95%CI 1.05–2.37; p = 0.028] under dominant model. Based on Trial of Org 10172 in Acute Stroke Treatment classification, an independent association of large vessel disease (LVD) was observed with the risk of IS under the dominant [OR = 2.09; 95% CI 1.17–3.75; p = 0.01] and recessive [4.09 95% CI 1.06–15.68; p = 0.04] models. All the observed genotype frequencies were in accordance with the Hardy–Weinberg equilibrium (HWE) in both cases and controls.

Conclusion: The findings of the present study suggest that polymorphism in G894T position of eNOS gene might be a risk factor for IS mainly for LVD stroke subtype in North Indian population. Further large prospective studies are required to confirm these findings.     

GNB3基因C825T多态性与缺血性脑卒中的关系

目的 了解G蛋白β亚基（GNB3）基因C825T多态性与北京地区缺血性脑卒中发病之间的关系。方法 利用PCR和分子杂交技术对北京地区294例缺血性脑卒中患者及280例非脑卒中患者的C825T多态性进行检测和分析。结果 C825T多态性位点在两组人群中的分布均符合Hardy-weinberg遗传平衡定律,缺血性脑卒中患者中CC、CT、TT三种基因型频率分布依次为30.27%、49.98%、20.75％,非脑卒中患者中为33.21%、47.50、19.29％,两组人群中825T等位基因频率分别为0.452和0.430,均无显著性差异。结论 GNB3基因C825T多态性与北京地区缺血性脑卒中发病无关。     

胰岛素受体基因多态性与缺血性脑血管病的关系

目的 探讨胰岛素受体（IR）基因突变在缺血性脑血管病发病中的作用。方法 以PCR－单链构像多态性（PCR－SSCP）法对68例动脉粥样硬化性血栓性脑梗死（ACI）患者、81例腔隙性脑梗死（LI）患者及62名健康对照者（HC）检测IR基因第17和20外子碱基变异情况。结果 IR基因第17外显子存在C、T两种等位基因,ACI患者突变型T等位基因频率显著高于对照者,且突变型患者血压及血糖、血脂代谢指标均显著高于野生型对照者,但相关分析显示IR基因多态性与血压变化无关;第20外子未发现有碱基变异。结论 IR基因第17外显子突变可能通过促动脉粥样硬化而参与缺血性卒中发病。     

白细胞介素-1受体拮抗剂基因多态性与缺血性卒中的关系

目的探讨存中国人群中，白细胞介素-1受体拮抗剂基因内含子2的变数串联重复（VNTR）多态性与缺血性卒中的关系。方法共收集了112例缺血性卒中患者（36例短暂性脑缺血发作．76例脑梗死）和105例年龄与性别相匹配的正常人或其他住院病人作为对照，通过聚合酶链反应（PCR）和琼脂糖凝胶电泳来确定其基因型。结果缺血性卒中患者A2等位基因频率要低于对照组（分别为0．049和0．105，X^2=4．78，P=0．029），A1／A2＋A2／A2基因型的频率也比对照组低（分别为0．098和0．200，X^2=4．47，P=0．035）。缺血性卒中亚组间的分析发现，短暂性脑缺血发作组与对照组的基因型及等位基因频率没有差别，而脑梗死组与对照组则有显著差别。脑梗死组A2等位基因频率明显低于对照组（分别为0．026和0．105，P=0．004，OR=0．23，95％CI为0．08-0．69）。结论白细胞介素-1受体拮抗剂内含子2基因VNTR多态性与缺血性卒中有关，其A2等位基因对缺血性卒中特别是脑梗死可能有保护作用。     

糖尿病与进展性缺血性脑卒中相关性研究

目的 探讨糖尿病与进展性缺血性脑卒中的相关性.方法 我院神经内科2006-05～2009-05收治的缺血性脑卒中患者130例为研究对象,其中伴糖尿病患者64例为糖尿病组,非糖尿病患者66例为非糖尿病组,比较2组发展为进展性缺血性脑卒中的差异.结果 糖尿病组64例中诊断为进展性卒中41例,占64.1%;非糖尿病组66例诊...     

Association of CHUK gene polymorphism and ischemic stroke in the Han Chinese population

BackgroundRecently, the pivotal role of component of inhibitor of nuclear factor kappa B kinase complex (CHUK) in lipid levels and blood pressure has been reported, and hypertension and hyperlipidemia are common risk factors of ischemic stroke (IS). However, the association between CHUK and IS has not yet been explored. This study aims at evaluating the relationship of CHUK polymorphisms (rs3808916, rs2230804 and rs3808917) and IS risk as well as IS-related risk factors. Methods: CHUK mRNA expression was detected between 53 IS patients and 53 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 816 IS patients and 816 age- and sex-matched healthy controls were genotyped using the Sequenom MassARRAY iPLEX platform. Results: CHUK mRNA was highly expressed in IS patients compared with healthy subjects (P＜0.001). No significant associations were observed between rs3808916, rs2230804, rs3808917 and IS susceptibility (P＞0.05). Moreover, haplotype analysis showed that no haplotype of CHUK polymorphisms was associated with IS (P > 0.05). However, rs2230804 was related to diastolic blood pressure (DBP) of IS patients (P = 0.035), while rs3808917 was associated with triglyceride (TG) levels (P = 0.046). Conclusions: The CHUK expression is involved in the development of IS. CHUK variants rs2230804, and rs3808917 may affect blood pressure and lipid levels of IS patients. However, CHUK rs3808916, rs2230804 and rs3808917 polymorphisms are not associated with IS risk.     

Association of the A1298C polymorphism in MTHFR gene with ischemic stroke

A meta-analysis was performed to assess the association between the methylenetetrahydrofolate reductase (MTHFR) A1298C genetic polymorphism and ischemic stroke. A comprehensive search was conducted to identify all case–control or cohort studies. The fixed or random effect pooled measure was selected based on the homogeneity between studies, as assessed by I². Meta-regression was used to explore the potential sources of between-study heterogeneity. Publication bias was estimated using Egger’s linear regression test. Thirteen case–control studies corresponded to the inclusion criteria comprising 2133 patients and 2572 controls which were included in the present meta-analysis. After excluding articles that deviated from Hardy–Weinberg equilibrium in controls and the key contributors to between-study heterogeneity, significant associations between MTHFR A1298C genetic polymorphism and risk of ischemic stroke were observed in dominant (odds ratio [OR] 1.227, 95% confidence interval [CI] 1.062–1.416) and codominant (OR 1.138, 95% CI 1.007–1.286) inheritance models. Moreover, in the subgroup analysis based on region (Asia and Europe), significant associations were observed in most genetic models in Asia but not in Europe. This meta-analysis suggests that MTHFR A1298C genetic polymorphism is associated with increased risk of ischemic stroke, and the C allele may be an important risk factor for ischemic stroke.     

神经源型一氧化氮合酶C276T基因多态性与抗抑郁疗效相关分析

目的探讨抑郁症患者血浆一氧化氮（NO）水平及神经源型一氧化氮合酶（nNOS）基因C276T多态性与抗抑郁剂疗效相关性。方法抑郁症患者予选择性5-羟色胺再摄取抑制剂（SSRIs）单药治疗8周,采用汉密尔顿抑郁量表（HAMD）评估患者抑郁症状严重程度;采用硝酸盐还原酶法测定正常对照组及抑郁症患者治疗前后血浆NO水平;全部受试者提取基因组DNA,并采用PCR-RFLP方法对nNOS基因C276T多态性进行基因分型。结果患者组疗前血浆NO水平为（76.8±31.6）μmol/L,显著高于疗后[（66.9±25.7）μmol/L,P=0.044]及正常对照组[（64.2±33.3）μmol/L,P=0.02],患者组疗后血浆NO水平为（66.9±25.7）μmol/L,与正常对照组（64.2±33.3）μmol/L相比差异无显著性（P=0.588）;患者组疗前HAMD评分为（24.3±4.3）分,疗后HAMD评分为（10.5±5.0）分,治疗前后HAMD减分率为（57.5±15.9）%;疗前血浆NO水平为（76.8±31.6）μmol/L,与疗前HAMD评分（24.3±4.3）分显著正相关（r=0.311,P=0.009）;nNOS基因可见两种等位基因条带C、T,组成三种基因型CC、CT、TT,携带不同基因型患者治疗前后HAMD评分和HAMD减分率差异无显著性（P〉0.05）。结论血浆NO浓度可能提示抑郁症急性发作期病情严重程度;nNOS基因C276T多态性可能不是影响抗抑郁剂治疗疗效的主要遗传因素。     

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。