NOS1基因多态性与腔隙性脑梗死相关性研究

目的:探讨神经元型一氧化氮合酶基因( NOS1)多态性与腔隙性脑梗死发病的关系。方法:本研究共纳入385例腔隙性脑梗死患者和313例对照组人群,以位于NOS1基因的rs9658281和rs2682820位点为遗传标记,采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)技术检测NOS1基因的多态性。结果:Cocaphase 分析表明腔隙性脑梗死组rs9658281位点G等位基因频率较对照组显著增高(x2 =4.135,P=0.042,OR=1.422,95％ CI 1.013～1.997),这种差异在女性患者更加明显(x2=9.522,P=0.002,OR=2.502,95％ CI 1.398～4.479)。卡方检验表明腔隙性脑梗死组rs9658281位点的GG基因型频率较对照组显著增高(x2=5.862,P=0.015,OR=1.579,95％ CI 1.091～2.286),这种差异在女性更加明显(x2=13.641,P＜0.0001,OR=3.501,95％CI 1.800～6.810)。经过多因素回归分析调整了传统危险因素的影响后,两组间的差异仍有显著性(P=0.014)。腔隙性脑梗死组和对照组的rs2682820位点的基因型、等位基因频率差异无显著性（P＞0. 05）。结论:NOS1基因rs9658281位点G等位基因与腔隙性脑梗死的发病可能有关。     

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...     

PPARγ基因多态性与动脉粥样硬化性脑梗死的相关性研究

目的 探讨PPARγ基因多态性与动脉粥样硬化性脑梗死的关系.方法 本研究共纳入227例动脉粥样硬化性脑梗死患者和404例健康对照人群.以rs1875796为遗传标记,应用多聚酶链-限制性片段长度多态性(PCR-RFLP)技术检测PPARγ基因rs1875796的个体基因型.结果 女性动脉粥样硬化性脑梗死组rs1875796的C等位基因频率较对照组明显增高(χ~2=9.113,P=0.003,OR=2.211,95%CI 1.321～3.700),女性动脉粥样硬化性脑梗死rsl875796位点的CC+CT基因型频率较对照组明显增高(χ=8.032,P=0.005,OR=2.404,95%CI 1.310～4.411),经过多因素回归分析调整了传统危险因素的影响,两组间仍有显著性差异(P=0.006).而男性动脉粥样硬化性脑梗死组与对照组rs1875796的等位基因、基因型频率差异无显著意义.结论 PPARγ基因可能与女性动脉粥样硬化性脑梗死相关.

Abstract：

Objective To investigate the genetic association between the PPARγ gene and atherosclerotic cerebral infarction. Methods 227 patients with atherosclerotic cerebral infarction were recruited into this study, and 404 healthy people were as controls. SNP rs1875796,a C to T base change located in intron 4 of the gene,was used as a genetic marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs 1875796 ( Hha I site). Results The frequcncy of allele C was significantly higher in female patients than controls(χ~2 =9. 113,P =0. 003,OR =2.211,95% CI 1. 321～3.700). And the frequcncy of genotype CC + CT was also significantly higher in female patients than controls(χ~2 = 8.032,P = 0.005,OR =2.404, 95% CI 1.310～4.411). Multiple factor regression analysis showed that the differences was still significant after adjusting the traditional risk factors of atherosclerotic cerebral infarction. The frequency of allele C,and genotype CC + CT showed no significance between male patients and controls. Conclusions The present study suggests that the PPARγ gene is likely to contribute to the etiology of atherosclerotic cerebral infarction in female Chinese.     

PPARγ基因多态性与2型糖尿病合并脑梗死的相关性研究

目的探讨PPARγ基因多态性与北方汉族人2型糖尿病合并脑梗死的关系。方法本研究共纳入791例受试对象,分成3组:健康对照组(NC)337例、单纯糖尿病组(T2DM)250例和糖尿病伴脑梗死组(T2DM CI)204例。以PPARγ基因rs1875796为遗传标记,应用多聚酶链-限制性片段长度多态性(PCR-RFLP)技术检测PPARγ基因rs1875796的基因型。结果女性T2DM CI组PPARγ基因rs1875796的C等位基因频率高于T2DM组、NC组(χ2=6.672,P=0.010,OR=1.991,95%CI 1.176~3.358和χ2=12.384,P<0.0001,OR=2.499,95%CI 1.500~4.162);女性T2DM CI组的CC CT基因型频率高于T2DM组、NC组(χ2=4.656,P=0.031,OR=2.008,95%CI 1.006~3.782和χ2=8.462,P=0.004,OR=2.486,95%CI 1.346~4.593)。经多因素回归分析调整了传统危险因素的影响后,女性T2DM CI组的CC CT基因型与T2DM组、NC组比较,差异仍有显著性(χ2=5.770,P=0.016,OR=2.713,95%CI 1.206~6.126)。结论PPARγ基因可能与女性2型糖尿病患者罹患脑梗死的发生有关。     

ABCA1基因R219K多态性与宁夏回、汉族脑梗死患者及血脂的关系

目的探讨宁夏回、汉族脑梗死患者与脂质代谢相关基因三磷酸腺苷结合盒转运子(ABCA1)的R219K多态性及血脂的关系。方法入选我院神经内科脑梗死住院患者266例,其中汉族患者185例(汉族脑梗死组)和回族患者81例(回族脑梗死组)。入院后检测血脂等生化指标,用PCR-RFLP方法测定R219K多态性,统计学方法分析酶切结果及其与血脂的关系。结果回、汉族脑梗死组ABCA1基因R219K基因型(RR、RK、KK)及等位基因频率(R、K)分别为28.4%、60.5%、11.1%,58.6%、41.4%;28.1%、46.5%、25.4%,51.4%、48.6%;汉族脑梗死组与回族脑梗死组等位基因频率分布无显著统计学差异(χ2=1.008,P=0.315),两组间基因型频率差异有统计学意义(χ2=7.647,P=0.022),与RK型比较,回族脑梗死组KK基因型较汉族脑梗死组低(χ2=7.657,P=0.006),将两组进行性别、年龄、高血压、糖尿病等因素亚组分析后,仅回族男性、高血压患者KK基因型较汉族脑梗死组低(χ2=6.725~7.127,P=0.008~0.010);各基因型间血脂水平无统计学差异(P>0.05...     

eNOS基因多态性与2型糖尿病并脑梗死的相关性研究

目的探讨内皮细胞性一氧化氮合酶(eNOS)基因内含子4上a／b基因的多态性与单纯2型糖尿病及2型糖尿病并脑 梗死(cerebral infarction,CI)的关系。方法应用聚合酶链反应(PCR)技术,检测89例2型糖尿病合并CI病人的基因型,并与对照组 比较。结果2型糖尿病合并CI组eNOS基因ab基因型的频率(26．97％)明显高于对照组(12．5％)及2型糖尿病组(12．68％),a等 位基因的频率(13．48％)也明显高于对照组(6．25％)及2型糖尿病组(6．34％),均有显著性差异(P<0．05)。结论eNOS基因ab 基因型与2型糖尿病合并CI有相关性,等位基因a可能是2型糖尿病合并CI的危险因素。     

PTGS1基因多态性与急性脑梗死患者阿司匹林抗血栓疗效的相关性

目的 探讨前列腺素内过氧化物合酶1(Prostaglandin-endoperoxide synthase1, PTGS1)基因多态性与急性脑梗死患者阿司匹林抗血栓疗效的相关性。方法 回顾性分析2017年10月-2020年10月在本院接受治疗的200例急性脑梗死患者的临床资料,按照其阿司匹林抗血栓疗效将其分为阿司匹林抵抗组(n=69)和阿司匹林敏感组(n=131),分析所有患者PTGS1基因多态性情况,比较2组性别、年龄、身体质量指数(Body Mass Index,BMI)、合并症(高血压病、冠心病、糖尿病)、PTGS1基因突变、不良嗜好(吸烟、酗酒)等临床特征及生化指标[血小板计数(Blood platelet,PLT)、超敏C反应蛋白(Hypersensitive-C reactive protein,hs-CRP)]水平,利用受试者工作特征(Receiver operating characteristic,ROC)曲线分析PLT,hs-CRP预测急性脑梗死患者阿司匹林抵抗的价值,将2组有差异的指标纳入Logistic回归分析模型,进行量化赋值,明确引起急性脑梗死患者阿司匹林抵抗的危险因素。结果 本研究200例急性脑梗死患者中PTGS1基因位点以AA为主,发生率为81.50%,其突变基因位点分别为AG,GG,占人数的14.00%、4.50%。阿司匹林抵抗组年龄≥60岁、合并糖尿病、PTGS1基因突变、吸烟患者的比例及PLT,hs-CRP水平显著高于阿司匹林敏感组(P<0.05)。经ROC曲线分析PLT,hs-CRP预测急性脑梗死患者阿司匹林抵抗的曲线下面积分别为0.879、0.866。年龄≥60岁、合并糖尿病、PTGS1基因突变、吸烟、PLT≥202.255×10⁹/L,hs-CRP≥24.695 mg/L是引起急性脑梗死患者阿司匹林抵抗的危险因素。结论 PTGS1基因多态性会增加急性脑梗死患者阿司匹林抵抗风险。除此之外,高龄、糖尿病、抽烟及PLT,hs-CRP异常高表达均可能影响阿司匹林抗血栓治疗效果。     

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.     

SORL1基因多态性与阿尔茨海默病的相关性研究

目的 探讨SORL1基因位点多态性与散发性阿尔茨海默病(Alzheimer’s disease, AD)之间的关联。方法 采用病例对照研究方法,通过PCR扩增技术及DNA测序检测法对新疆地区131例散发性AD患者和128例健康对照组的SORL1基因的SNP位点rs1010159、rs2282649、rs3824968、rs1699102、rs3781836、rs2070045、rs3781834、rs641120、rs689021、rs668387、rs12364988、rs985421的多态性进行对比分析。结果 SORL1基因的SNP位点rs1010159、rs2282649、rs3824968、rs1699102、rs3781836、rs2070045、rs3781834、rs641120、rs689021、rs668387、rs12364988、rs985421的多态性在AD组与对照组中差异无统计学意义(P>0.05)。结论 SORL1基因的SNP位点rs1010159、rs2282649、rs3824968、rs1699102、rs3781836、rs2070045、rs...     

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。     

Investigation of a neuronal nitric oxide synthase gene (NOS1) polymorphism in a multiple sclerosis population

Multiple Sclerosis (MS) is a chronic neurological disease characterized by demyelination associated with infiltrating white blood cells in the central nervous system (CNS). Nitric oxide synthases (NOS) are a family of enzymes that control the production of nitric oxide. It is possible that neuronal NOS could be involved in MS pathophysiology and hence the nNOS gene is a potential candidate for involvement in disease susceptibility. The aim of this study was to determine whether allelic variation at the nNOS gene locus is associated with MS in an Australian cohort. DNA samples obtained from a Caucasian Australian population affected with MS and an unaffected control population, matched for gender, age and ethnicity, were genotyped for a microsatellite polymorphism in the promoter region of the nNOS gene. Allele frequencies were compared using chi-squared based statistical analyses with significance tested by Monte Carlo simulation. Allelic analysis of MS cases and controls produced a chi-squared value of 5.63 with simulated P = 0.96 (OR(max) = 1.41, 95% CI: 0.926-2.15). Similarly, a Mann-Whitney U analysis gave a non-significant P-value of 0.377 for allele distribution. No differences in allele frequencies were observed for gender or clinical course subtype (P > 0.05). Statistical analysis indicated that there is no association of this nNOS variant and MS and hence the gene does not appear to play a genetically significant role in disease susceptibility.     

Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia

Nitric oxide (NO) has been identified as a widespread and multifunctional biological messenger molecule in the central nervous system (CNS), with possible roles in neurotransmission, neurosecretion, synaptic plasticity, and tissue injury in many neurological disorders, including schizophrenia. Neuronal NO is widely produced in the brain from L-arginine catalyzed by neuronal NO synthase (NOS1). We therefore hypothesized that the NOS1 gene may play a role in the pathophysiology of schizophrenia. In the present study, we examined the genetic association between a novel single nucleotide polymorphism (SNP: a C-->T transition located 276 base pairs downstream from the translation termination site) of the human NOS1 gene, which is located in chromosome 12q24, and schizophrenia (215 Japanese patients with schizophrenia and 182 healthy controls). The allele frequencies of the polymorphism in exon 29 of the NOS1 gene differed significantly between patients with schizophrenia and controls (chi(2) = 20.10, df = 1, P = 0.000007; relative risk = 1.92; 95% confidence interval = 1.44-2.55). Our results suggest that the NOS1 gene polymorphism may confer increased susceptibility to schizophrenia.     

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。     

Absence of linkage with the neuronal nitric oxide synthase (NOS1) gene in 41 multiplex Swedish MS families

Several genetic factors are likely to play a role in the aetiology of multiple sclerosis (MS), although so far only the HLA gene complex has been clearly identified as important. In addition, several studies support the importance of nitric oxide synthase (NOS) as a component in the pathogenesis of MS. We have investigated the role of the neuronal nitric oxide synthase (NOS1) gene in 41 Swedish multiplex MS families by parametric and nonparametric linkage analysis with two polymorphic intragenic markers. Two-point lod scores were clearly negative, effectively excluding a role of the NOS1 gene in most models tested. Non-parametric linkage analysis (NPL), affected pedigree member (APM) analysis and extended transmission disequilibrium test (ETDT) also failed to provide evidence for a susceptibility locus in this gene. Thus, a contribution of the NOS1 gene to the genetic background of MS is unlikely in this 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.     

Investigation of an inducible nitric oxide synthase gene (NOS2A) polymorphism in a multiple sclerosis population

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting most commonly the Caucasian population. Nitric oxide (NO) is a biological signaling and effector molecule and is especially important during inflammation. Inducible nitric oxide synthase (iNOS) is one of the three enzymes responsible for generating NO. It has been reported that there is an excessive production of NO in MS concordant with an increased expression of iNOS in MS lesions. This study investigated the role of a bi-allelic tetranucleotide polymorphism located in the promoter region of the human iNOS (NOS2A) gene in MS susceptibility. A group of MS patients (n = 101) were genotyped and compared to an age- and sex-matched group of healthy controls (n = 101). The MS group was subdivided into three subtypes, namely relapsing-remitting MS (RR-MS), secondary-progressive MS (SP-MS) and primary-progressive MS (PP-MS). Results of a chi-squared analysis and a Fisher's exact test revealed that allele and genotype distributions between cases and controls were not significantly different for the total population (chi(2) = 3.4, P(genotype) = 0.15; chi(2) = 3.4, P(allele) = 0.082) and for each subtype of MS (P > 0.05). This suggests that there is no direct association of this iNOS gene variant with MS susceptibility.     

Variants in the neuronal nitric oxide synthase (nNOS,NOS1) gene are associated with restless legs syndrome

Sixty percent of the patients with restless legs syndrome (RLS) report a positive family history. To date five loci have been mapped on chromosome 12q, 14q, 9p, 2q, and 20p (RLS1‐5) but no gene has been identified so far. To identify genes related to RLS, we performed a three‐stage association study (explorative study, replication study, high‐density mapping) in two Caucasian RLS case‐control samples of altogether 918 independent cases and controls. In the explorative study (367 cases and controls, respectively), we screened 1536 SNPs in 366 genes in a 21 Mb region encompassing the RLS1 critical region on chromosome 12. Armitage trend test revealed three genomic regions that were significant (P < 0.05). In the replication study (551 cases and controls, respectively) we genotyped the most significant SNPs of Stage 1. After correction for multiple testing, association was observed with SNP rs7977109 (P_nominal = 0.00175, P_{Westfall‐Young} = 0.04895, OR = 0.76228, 95% CI = 0.64310–0.90355), which is in the neuronal nitric oxide synthase (NOS1) gene. High‐density mapping using altogether 34 tagging and coding SNPs of the NOS1 gene in both case‐control samples further confirmed the significant association results to NOS1. Ten more SNPs revealed significance with nominal P‐values from 0.0001 to 0.0482 (genotypic test and Armitage test). Altogether, this study provides evidence for an association of variants in the NOS1 gene and RLS, and suggests the involvement of the NO/arginine pathway in the pathogenesis of RLS. Potential usage of NO modulating agents as new treatment options for RLS have become a challenging aspect for future research of this disorder. © 2007 Movement Disorder Society