内皮细胞性一氧化氮合酶基因多态性与缺血性脑卒中的相关性研究

目的　探讨大连地区汉族人内皮细胞性一氧化氮合酶 (ecNOS)基因多态性与缺血性脑卒中的关系。方法　应用聚合酶链反应对 170例缺血性脑卒中群体及 90例非脑血管病群体ecNOS基因第 4号内含子多态性进行分析。结果　在缺血性脑卒中组中 ,高血压、糖尿病、吸烟、纤维蛋白原、颈内动脉狭窄与对照组比较 ,有显著性差异 (均P <0 .0 5 )。非条件性Logistic回归分析证实 ,ecNOS基因多态性不是缺血性脑卒中的独立危险因素。结论　ecNOS 4a/b基因多态性与大连地区汉族人缺血性脑卒中无相关性     

内皮型一氧化氮合酶基因+894G/T多态性与偏头痛发病的meta分析

目的分析内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)基因+894G/T多态性与偏头痛发病风险之间的相关性。方法本研究检索时间从建库至2016年10月。纳入评估eNOS多态性(+894G/T)与偏头痛发病风险之间相关性的病例对照研究。初筛得到365篇全文,经筛选后最终5篇纳入meta分析。异质性分析采用I~2检验,文献质量评估采用英国牛津循证医学中心文献严格评价项目。结果与GG+GT基因型相比,TT基因型增加有先兆偏头痛(migraine with aura,MA)的发生风险(OR=1.56,95%CI 1.11~2.20;I~2=0%,P=0.01)。在非高加索人群中,GT+TT基因型可增加偏头痛发病风险(OR=1.53,95%CI 1.08~2.16;I~2=0%,P=0.02)。结论本研究提示内皮型一氧化氮合酶基因+894G/T多态性与偏头痛发病风险之间有一定的关系,并且可能因人群遗传背景的不同与偏头痛亚型有一定关联。     

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。     

内皮型一氧化氮合酶基因第4内含子基因多态与福建汉族脑血管病的相关性

目的 研究福建汉族人内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)基因第4内含子27 bp可变串联重复序列(variable number of tandem repeat,VNTR)与脑血管病关系.方法 依据缺血性卒中TOAST(Trial of ORG 10172 in Acute Stroke Treatment)分型收集132例大动脉粥样硬化性卒中(large artery atherosclerosis,LAA),63例腔隙性脑梗死(lacunar infarction,LI)及62例高血压性脑出血患者为病例组,同时选择年龄、性别匹配的237名健康者为对照组,采用聚合酶链反应结合2%琼脂糖电泳技术检测eNOS基因第4号内含子27 bp VNTR的多态性.结果 正常福建汉族人eNOS基因第4内含子除bb,ab,aa基因型外,尚出现罕见的bc基因型,其基因型频率分别为0.789,0.203,0.004,0.004;b、a、c等位基因频率分别为.892,0.106及0.002.LAA及LI患者27 bp VNTR多态与对照组差别无统计学意义,LAA组bc基因型频率(0.030)虽明显高于对照组(0.004),但差异无统计学意义;缺血性卒中伴/不伴高血压病与该基因多态无相关性.高血压性脑出血患者的aa基因型频率为0.048.明显高于bb+ab基因型(OR=11.42,95% CI:1.209-117.892,P<0.05).结论 eNOS第4内含子aa基因型可能是福建汉族人高血压性脑出血的遗传危险因素,但该位点多态性与福建汉族LAA及LI无相关性.     

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.     

中国人内皮型一氧化氮合酶基因G894T多态性与脑梗死相关性的Meta分析

目的综合评价中国人内皮型一氧化氮合酶基因G894T(Glu298Asp)多态性与脑梗死的关系。方法搜集国内外公开发表的有关中国人内皮型一氧化氮合酶基因G894T多态性与脑梗死关系的研究文献,剔除不符合要求的文献,应用Meta分析软件RevMan5.1,对各研究结果进行异质性检验及数据合并,应用RevMan5.1和Stata11.0评估发表偏倚。结果共有11篇文献纳入Meta分析,累计病例组1768例,对照组1818例。合并基因型(GT+TT)/GG的OR值为1.46,95%CI为1.24～1.73(P<0.00001),合并基因型TT/GG的OR值为2.18,95%CI为1.32～3.61(P=0.002),合并基因型GT/GG的OR值为1.41,95%CI 1.18～1.67(P=0.0001),合并等位基因T/G的OR值为1.65,95%CI 1.28～2.12(P=0.0001)。结论中国人内皮型一氧化氮合酶基因G894T(Glu298Asp)多态性与脑梗死的发病具有相关性。携带基因型TT、GT及等位基因T可增加患脑梗死的风险。     

精神分裂症患者一级亲属的探索性眼球运动与eNOS基因G894T多态性研究

目的：探讨内皮型一氧化氮合成酶（eNOS）基因G894T多态性与精神分裂症患者一级亲属探索性眼球运动（EEM）缺陷的相关性。方法：共收集精神分裂症患者一级亲属193名,正常对照家系一级亲属150名,进行EEM检查,并采用基因芯片技术进行eNOS基因型检测。结果：精神分裂症一级亲属EEM异常率（52%）显著高于正常对照家系一级亲属EEM异常率（15%）（χ^2=52,P〈0.01）;EEM异常者与EEM正常者eNOS基因GT＋TT基因型频率及T等位基因频率差异无显著性（χ^2=2.08,P〉0.05;χ^2=2.55,P〉0.05）。在101名精神分裂症一级亲属的EEM异常者中,对30名GT＋TT基因型携带者与71名GG基因型携带者的凝视点数（NEF）、反应性探索评分（RSS）比较,差异均无显著性（P均〉0.05）。结论：eNOS基因G894T多态性与精神分裂症患者一级亲属的EEM缺陷可能无关。     

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.     

Inflammatory system gene polymorphism and the risk of stroke: a case-control study in an Indian population

Sequence variations in genes involved in inflammation system are known to contribute to the risk of cardiovascular diseases (CVD) including stroke. In this study, we performed a genetic association study on the single nucleotide polymorphisms (SNPs) present in the genes CD14 (-159 C/T), TNFalpha (-308 G/A), IL-1alpha (-889 C/T), IL-6 (-174 G/C), PSMA6 (-8 C/G), and PDE4D (SNP83 T/C, respectively) in order to discern their possible role in the susceptibility to stroke in a North Indian population. These SNPs were previously found to be associated with CVD through their contribution to inflammation. A case-control design was used to examine 176 stroke patients (112 ischemic and 64 hemorrhagic stroke patients) and 212 unrelated healthy control individuals. After adjustment for the confounding risk factors, the IL-1alpha -889 T allele carriers (TT+CT) were found to be strongly associated with both forms of stroke (OR=2.56; 95% CI=1.53-4.29; P=0.0004). The CC genotype of PDE4D was found to be associated only with ischemic stroke (OR=2.02; 95% CI=1.08-3.76; P=0.03). None of the variants tested for the CD14, TNFalpha, IL-6, and PSMA6 genes found to confer risk for stroke in the study population. In conclusion, the -889 C/T and SNP83 T/C SNPs of the IL-1alpha and PDE4D genes, respectively, appear to be genetic risk factors for stroke in our study population.     

Endothelial nitric oxide synthase Glu298Asp, 4b/a,and −786T>C gene polymorphisms and the risk of ischemic stroke

Saidi S, Mallat SG, Almawi WY, Mahjoub T. Endothelial nitric oxide synthase Glu298Asp, 4b/a, and ?786T>C gene polymorphisms and the risk of ischemic stroke
Acta Neurol Scand: 2010: 121: 114–119.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background and purpose – Endothelial nitric oxide synthase (eNOS) gene polymorphisms were associated with reduced NO production, and were evaluated as risk factors for ischemic stroke (IS). We investigated the association between eNOS gene ?786T>C (promoter), 27‐bp repeat 4b/4a (intron 4), and Glu298Asp (exon 7) polymorphisms with IS in 329 IS patients and 444 controls. Materials and methods – Glu298Asp and ?786T>C genotyping was done by PCR‐RFLP, 4b/4a was assessed by PCR–ASA. The contribution of eNOS polymorphisms to IS was analyzed by haplotype and multivariate regression analysis. Results – Higher frequency of 298Asp allele was seen in IS patients (P = 1.2 × 10^?10), which remained independently associated with IS on multivariate analysis after controlling for traditional cerebrovascular risk factors. Allele and genotype distribution of 4b/4a and ?786T>C polymorphisms were comparable between patient and controls. Significantly higher prevalence of 298Asp/4b/?786T and 298Asp/4b/?786C haplotypes were seen in IS cases, thus conferring a disease susceptibility nature to these haplotypes. Multivariate regression analysis confirmed the association of 298Asp/4b/?786T and 298Asp/4b/?786C haplotypes, and in addition identified 298Asp/4a/?786T haplotype to be independently associated with IS, after controlling for traditional cerebrovascular risk factors. Conclusions – Genetic variation at the eNOS locus represent genetic risk factor for increased susceptibility to IS.     

Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of venous thromboembolism in Chinese population

Introduction

Endothelium derived nitric oxide (NO) is a key mediator of vascular homeostasis. Endothelial nitric oxide synthase (eNOS) gene, by affecting the expression and functional activity of the eNOS enzyme, thereby reducing NO availability, may be implicated in venous thromboembolism (VTE). We investigated the eNOS G894T polymorphism in VTE patients in the Chinese population.

Materials and methods

A case-control study was conducted in a general hospital. Blood samples, collected from 462 consecutive patients with VTE and 462 healthy controls, were used for DNA extraction. Single nucleotide polymorphisms (SNP) of eNOS (894 G/T) were determined by allele specific-polymerase chain reaction (ARMS-PCR) analysis.

Results

The eNOS 894 G/T polymorphism alleles distribution was in agreement with the principle of Hardy-Weinberg equilibrium. The prevalence of homozygote, heterozygote and pathological homozygote for the eNOS G894T polymorphism in VTE patients was 79.7%, 18.1% and 2.2%, respectively (controls: 86.6%,12.3% and 1.1%). T allele distribution in the VTE (11.3%) and especially the male VTE patients (12.5%) was more common than in healthy controls (7.3%). The frequency of GT + TT genotype was significantly higher among the age ≤ 55 years patients in VTE group than in controls (20.1% vs. 12.2%, P = 0.033).

Conclusion

Our result demonstrates that the 894 G/T polymorphism variant of eNOS is a risk factor for VTE in Chinese population.     

诱导型一氧化氮合酶基因多态与脑卒中合并冠心病

目的 探讨诱导型一氧化氮合酶(NOS)2A基因多态与脑卒中合并冠心病发病的关系.方法 以rs28944190位点为遗传标记,采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)检测708例脑卒中患者和235名对照组人群NOS2A基因的多态性.结果 脑卒中组和对照组的rs28944190位点等位基因、基因型频率差异无统计学意义;以是否合并冠心病对病例组人群进行分层后,cocaphase分析表明合并冠心病的脑卒中组rs28944190位点的C等位基因频率(23.9%)较单纯脑卒中组(16.6%)明显增高(x2=5.629,P=0.018,OR=1.580,95%CI 1.083～2.306),这种差异在男性患者更加明显(x2=8.592,P=0.003,OR=1.983,95%CI 1.255～3.134).卡方检验表明合并冠心病的脑卒中组AC+CC基因型的频率(47.9%)明显高于单纯脑卒中组(30.8%,x2=10.761,P=0.001,OR=2.065,95%CI 1.34～3.19),在男性患者差异更加明显(x2=15.762,P=0.000,OR=2.985,95%CI 1.74～5.12).结论 NOS2A基因与脑卒中的发病可能无关,但可能与合并冠心病的脑卒中发病相关.     

神经源型一氧化氮合酶C276T基因多态性与抑郁症相关分析

目的测定抑郁症患者抗抑郁剂治疗前后血浆一氧化氮（NO）水平变化,旨在探讨神经源型一氧化氮合酶（nNOS）基因C276T多态性与血浆NO浓度及抑郁症发病相关性。方法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;全部受试者取全血标本提取基因组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],两组疗后血浆NO水平相比差异无显著性（P=0.588）;根据PCR-RFLP结果,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,两组等位基因及基因型分布频率差异无显著性（均P〉0.05）,且携带不同基因型者之间血浆NO水平差异亦无显著性（均P〉0.05）。结论血浆NO浓度增高可能是抑郁症发病的影响因素;nNOS基因C276T多态性可能不直接影响血浆NO浓度,也不是抑郁症发病的主要基因因素。     

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。     

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。     

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     

Association between lymphotoxin alpha (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke in North Indian population: a hospital-based case-control study

Purpose: Lymphotoxin alpha (LTA), a proinflammatory cytokine, plays an important role in promoting atherosclerosis which is an independent risk factor for stroke. Recent genetic studies have suggested that polymorphisms in the LTA gene, which affect its expression and biological function, may contribute to the development of stroke. The aim of this case-control study was to determine the association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. Methods: Genotyping was determined by using SNaPshot method for 250 ischemic stroke (IS) patients, 250 age and sex matched IS free controls, 100 intracerebral hemorrhage (ICH) patients and 100 age and sex matched ICH free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of stroke. The linkage disequilibrium (LD) was analyzed by using HaploView 4.2 software. Results: The distribution of LTA (-252 A/G and -804 C/A) genotypes was consistent with Hardy–Weinberg equilibrium. Adjusted conditional logistic regression analysis showed no significant association between LTA (-252 A/G and -804 C/A) gene polymorphisms and risk of both IS and ICH. Based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, a significant association between LTA -252 A/G gene polymorphism and small vessel disease subtype of IS under dominant model (OR, 2.06; 95% CI, 1.03–4.12; p value 0.04) with the risk of IS was observed. No LD was observed for both single nucleotide polymorphisms (SNPs) in north Indian population. Conclusion: Neither -252 G/A nor -804 C/A polymorphism of the LTA gene was found to be associated with overall stroke as well as any subtype of IS excluding SVD in North Indian population.