肾素基因G10631A和血管紧张素原基因C521T多态性与脑梗死的关系

目的 研究肾素(PEN)基因G10631A、血管紧张素原(AGT)基因C521T多态性与脑梗死的关系.方法 采用聚合酶链式反应.限制性片段长度多态性(PCR-RFLP)方法检测82例脑梗死患者和89名正常对照者的REN基因10631位点、AGT基因521位点的多态性,并用Logistic回归分析两基因多态性与脑梗死的关系.观察两组基因单倍型的分布.结果 脑梗死组REN基因10631从基因型(31.7%)、A等位基因(49.4%).ACT基因521TT基因型(22.0%)、T等位基因频率(28.0%)显著高于正常对照组(10.1%、30.3%、6.7%、11.8%)(均P<0.05).Logistic回归分析显示,REN基因10631AA基因型、AGT基因521TT基因型增加脑梗死的发生概率,发病的相对危险度(OR)分别为2.798、3.492(均P<0.05).脑梗死组基因单倍型521T-10631A的分布频率明显高于正常对照组(P<0.005).结论 REN基因10631AA基因型和A等位基因、AGT基因521TT基因型和T等位基因可能为脑梗死的易患因素;单倍型521T-10631A可能是脑梗死发病的遗传危险因素.     

肾素基因A10631G多态性与大动脉粥样硬化性脑梗死的相关性研究

目的探讨肾素基因A10631G多态性与大动脉粥样硬化性(LAA)脑梗死的相关性。方法收集LAA脑梗死患者110例、原发性高血压(EH)患者105例及人群对照组112例,运用聚合酶链反应-限制性酶切技术(PCR-RFLP)分析肾素基因A10631G多态性与LAA脑梗死,及其与EH的相关性,并用Logistic回归分析该位点多态性与CI的关系。结果 LAA脑梗死组与对照组相比,高血压病构成比、总胆固醇水平、高同型半胱氨酸血症(Hhcy)构成比、低密度脂蛋白水平差异有显著性(P0.05);AA型,AG型,GG型基因型分布差异有显著性(P0.01);A及G等位基因频率在两组分布无显著性差异(P=0.55)。EH组与对照组相比,三种基因型及等位基因频率分布差异无显著性(P0.05)。Logistic回归分析显示A10631G基因型未被纳入回归方程。结论 REN基因A10631G位点多态性与EH的发生无明显相关性,与LAA脑梗死的发生相关,但是回归分析并未证实该位点多态性是LAA脑梗死的独立危险因素。     

新疆哈萨克族内皮细胞蛋白C受体基因多态性与脑梗死的相关性

目的探讨新疆哈萨克族内皮细胞蛋白C受体(EPCR)A6936G基因多态性与脑梗死的相关性。方法运用PCR-限制性片段长度多态性(RFLP)技术检测80例哈萨克族脑梗死患者(脑梗死组)及100名哈萨克族对照者(对照组)EPCR A6936G基因型和等位基因频率。结果脑梗死组出现AA、AG、GG基因型,对照组出现AA、AG基因型;脑梗死组AG+GG基因型及G等位基因频率显著高于对照组(均P<0.05)。结论 EPCR A6936G多态性可能与哈萨克族脑梗死的发生有一定的关系。     

载脂蛋白M基因多态与脑梗死的相关性

目的 探讨中国北方汉族人群载脂蛋白M(ApoM)基因多态与脑梗死的关系.方法 采用聚合酶链反应(PCR)扩增基因组DNA直接测序法结合PCR-限制性片段长度多肽(RFLP)方法检测560例脑梗死和550名健康对照的ApoM基因多态,发现1号内含子rs805264、5号内含子rs707922及rs707921 3个单核苷酸多态位点.结果 脑梗死组ApoM基因rs805264位点GA+AA型及A等位基因频率、rs707922位点GT+TT型及T等位基因频率、rs707921位点CA+AA型及A等位基因频率均明显高于对照组.ApoM基因rs805264、rs707922和rs707921 3个多态位点存在显著连锁不平衡,三座位等位基因G-G-C紧密连锁,A-T-A紧密连锁(χ2=2595.03,P<0.01).3个位点的每对之间均存在强连锁不平衡(D′=0.972～0.992).Logistic回归分析显示,A-T-A单体型与脑梗死明显相关(OR= 1.780, 95% CI 1.333～ 2.376,P<0.01).结论 ApoM基因rs805264位点GA基因型及A等位基因、rs707922位点GT基因型及T等位基因、rs707921位点CA基因型及A等位基因与脑梗死密切相关.ApoM基因A-T-A单体型可能与脑梗死遗传致病有关.     

难治性精神分裂症与亚甲基四氢叶酸还原酶基因多态性的关联分析

目的:探讨难治性精神分裂症与亚甲基四氢叶酸还原酶(MTHFR)基因C677T和A1298C多态性的关系。方法:应用聚合酶链反应-限制性片断长度多态性方法(PCR-RFLP)检测102名正常对照、138例难治性精神分裂症患者及97例非难治性精神分裂症患者MTHFR基因的C677T和A1298C多态性。结果:患者组与对照组,难治组与非难治组C677T、A1298C基因型分布差异均无统计学意义(C677T,χ2=4.83,P=0.09;χ2=1.90,P=0.39;A1298C,χ2=1.50,P=0.47;χ2=3.90,P=0.14),而患者组C677T的T等位基因频率显著高于正常对照组(P=0.04),难治组A1298C的C等位基因频率显著高于非难治组(P=0.04)。677TT/1298AA、677CT/1298AC复合基因型患病相对风险度比677CC/1298AA型显著提高(OR=4.13,95%CI=1.26～13.58,P=0.02;OR=2.95,95%CI=1.23～7.07,P=0.01),而在难治组和非难治组中,复合基因型差异无统计学意义。结论:MTHFR基因677T等位基因和677TT/1298AA、677CT/1298AC复合基因型是精神分裂症发病危险因素,MTHFR基因1298C等位基因可能是难治性精神分裂症的危险因子之一。     

沉默信息调节基因2的microRNA结合位点多态性与散发帕金森病的相关性研究

目的探讨沉默信息调节基因2(Sirtuin 2)3’UTR的microRNA结合位点多态性与散发帕金森病(Parkinson’s disease,PD)的关系。方法采用病例-对照研究、聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析了83例PD患者(PD组)与101例健康成人(对照组)Sirtuin 2基因3’UTR G+281A位点多态性。结果 PD组Sirtuin 2基因3’UTR的miRNA-486-3p结合位点(3’UTR G+281A位点)A等位基因频率以及GA+AA基因型频率高于对照组,但两组差异无统计学意义(P>0.05);在女性PD组A等位基因携带者的频率较对照组高,经χ2检验提示有相关倾向(χ2=3.205,P=0.073);PD组出现两例AA基因型,而对照组则无此种基因型。结论 Sirtuin 2基因3’UTR G+281A多态性的纯合子AA可能是PD的遗传易感性基因型,而在女性A等位基因携带者PD患病的风险可能增加。     

GAS6基因内含子834+7G/A位点多态性与脑梗死的相关性研究

目的 探讨粤西地汉族人群中GAS6基因(生长停滞特异性基因6)内含子834+7G/A位点的单核苷酸多态性(SNP)与脑梗死的相关性.方法 应用聚合酶链反应—限制性内切酶片段长度多态性分析方法 (PCR- RFLP)检测180例梗死患者和150例对照组的GAS6基因内舍子SNP 834+7G/A的基因型.结果 病例组G等位基因携带者的频率为97.8％,AA基因型的频率为2.2％,而在对照组分别为92.0％和8.0％,两组相比较差异有统计学意义(x2=5.920,P=0.015),G等位基因携带者发生脑梗死的风险是AA基因型的3.933倍(OR =3.933,95％ CI:1.117～13.848,P=0.033).结论 GAS6基因内舍予SNP834+7G/A的基因多态性与粤西地区汉族人脑梗死相关,G等位基因携带者增加脑梗死的发病风险,而AA基因型可能对脑梗死有保护作用.     

长沙地区汉族人群apoB基因多态性与脑梗死的关系研究

目的探讨湖南长沙地区汉族人群载脂蛋白B(apolipoprotein B,apoB)G12669A、C7673T多态性与脑梗死的关系。方法采用聚合酶链反应-限制性片段长度多态性分析法分别检测130例脑梗死患者和100例正常对照的apoB基因G12669A、C7673T多态等位基因频率。结果湖南长沙地区汉族人群存在apoB基因G12669A、C7673T多态性,脑梗死组中apoB基因G12669A、C7673T多态等位基因频率G/A为0.904/0.096,C/T为0.881/0.119,在正常对照G/A为0.955/0.045,C/T为0.960/0.040;脑梗死组apoB基因G12669A多态A等位基因频率及C7673T多态T等位基因频率均显高于正常对照组(P<0.05,P<0.01)。结论apoB G12669A多态A等位基因可能是湖南长沙地区汉族人群脑梗死发病的遗传易感因素。     

Sirtuin 2基因的Intron8多态性与散发帕金森病的相关性研究

目的探讨中国汉族人群Sirtuin 2基因Intron8（rs7257949A/T）多态性与散发帕金森病（PD）的关系。方法采用病例-对照研究、聚合酶链反应--限制性片段长度多态性（PCR-RFLP）方法分析了82例PD患者（PD组）与103例健康成人（对照组）Sirtuin 2基因rs7257949A/T位点多态性。结果病例组SIRT2基因rs7257949A/T多态性的AA基因型20.7%（17/82）,T等位基因携带者为79.3%（65/82）;而对照组分别为AA型7.8%（8/103）,T等位基因携带者为92.2% （95/103）。经χ2检验两组之间的差异有统计学意义（χ2=6.566,P=0.010）。病例组A、T等位基因频率分别为48.6%（70/144）,51.4%（74/144）;对照组A、T等位基因频率分别为34.0%（70/206）,66.0%（136/206）。经χ2检验两组之间的差异有统计学意义（χ2=7.559,P=0.006）。结论中国汉族人群Sirtuin 2基因Intron8（rs7257949A/T）多态性的纯合子AA可能是PD的遗传易感性基因型。     

血管紧张素原基因M235T及α-内收蛋白基因G460T多态性与脑梗死的关系

目的 探讨血管紧张素原(AGT)基因M235T及α-内收蛋白基因G460T多态性与脑梗死的关系.方法 采用PCR-限制性片段长度多态性(RFLP)方法检测396例脑梗死患者(脑梗死组)和360名健康体检者(正常对照组)AGT基因M235T及α-内收蛋白基因G460T基因型及等位基因频率,分析其与脑梗死的关系.结果 (1)脑梗死组AGT MM基因型频率明显低于正常对照组,MT基因型频率明显高于正常对照组(均P ＜0.05);两组间等位基因频率差异无统计学意义.(2)两组间α-内收蛋白G460T基因型及等位基因频率差异无统计学意义.(3)脑梗死组MM+ GG频率显著少于正常对照组(P＜0.05).结论 AGT基因MT基因型可能与脑梗死发病有关;α-内收蛋白基因G460T多态性可能与脑梗死的发病无关;MM +GG基因型组合可能为脑梗死发病的保护因素.     

趋化因子受体CX3CR1基因多态与中国北方人群脑梗死的关系

目的探索趋化因子受体CX3CR1基因单核苷酸多态(SNPs)与中国北方人群脑梗死发病的关系。方法不同类型的脑梗死患者563例及健康对照563例,周围静脉全血提取单个核细胞基因组DNA并行PCR分段扩增CX3CR1基因。抽取其中各200例进行CX3CR1基因测序,明确脑梗死组和对照组的SNP情况。两组剩下的各363例针对查到的SNP位点设计引物,将包含SNP位点的局部片段进行PCR及基因测序以检测SNP情况。结果发现研究人群有rs3732379(C→T)、rs3732378(G→A)、rs1050592(T→C)3个SNP位点。其中脑梗死组rs3732379位点T碱基及TT、TC基因型,rs3732378位点A碱基及AA、GA型,rs1050592位点C碱基及CC、TC型的频率均明显高于对照组。rs3732379、rs3732378、rs1050592间有显著的连锁不平衡,形成3种单倍型(按前述3个SNP的三座位碱基顺序,分别为T-A-C、T-G-C、C-G-T)及6种基因型。单倍型分析显示:单倍型T-A-C的频率与脑梗死的发病相关(OR=5.24,P=0.002)。结论在中国北方人群中,携带rs3732379位点T碱基及TT、TC型,rs3732378位点A碱基及AA、GA型,rs1050592位点C碱基及CC、TC型与脑梗死的发病相关,携带单倍型T-A-C是脑梗死发病的危险因素。     

缺血性脑梗死患者血清同型半胱氨酸水平与性别、高血压、亚甲基四氢叶酸还原酶基因的关系

目的探讨同型半胱氨酸(Hcy)水平与性别、高血压和亚甲基四氢叶酸还原酶(MTHFR)基因的关系。方法检测229例脑梗死患者和111例非脑梗死患者的血清Hcy水平和MTHFR基因型,比较血清Hcy在不同性别、高血压及MTHFR基因型患者之间的差别。结果脑梗死组T等位基因频率显著高于非脑梗死组(χ^2=4.98,P=0.026)。脑梗死组中,TT基因型患者的Hcy水平显著高于CC和CT基因型患者(P<0.05~0.01)。非脑梗死组中,TT基因型患者的Hcy水平显著高于CC和CT基因型的患者(均P<0.01)。脑梗死组CC、CT、TT基因型患者的Hcy水平均显著高于非脑梗组(t=4.21,P<0.01;t=4.20,P<0.01;t=2.20,P=0.033)。两组间高血压患者的Hcy水平均显著高于无高血压患者(均P<0.01),男性Hcy水平均显著高于女性(均P<0.01)。结论脑梗死患者具有较高的T等位基因频率。TT基因型、男性、高血压患者具有较高的Hcy水平。     

Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset

Evidence suggests that interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites -1082 (A/G) and -819 (C/T) in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction (cerebral infarction group) and 115 healthy subjects (control group). We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups (χ² = 6.643, P = 0.010). The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group (92.3%) than in the control group (86.1%) (P = 0.015). Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype (OR = 2.031, 95%CI: 1.134–3.637). In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction (OR = 2.073, 95%CI: 1.278–3.364). No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups (P > 0.05). These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.     

血管紧张素原基因M235T和T174M多态性与脑梗死的相关性研究

目的:探讨血管紧张素原((Angiotensinogen,AGT)基因M235T和T174M多态性与原发性高血压及脑梗死发生的相关性。方法:采用聚合酶链反应-限制性片断长度多态性分析(PCR-RFLP)对82例脑梗死患者、78例原发性高血压患者及82例人群对照进行AGT基因M235T和T174M多态性分析。结果:AGT M235T和T174M多态性在原发性高血压组与正常对照组分布有显著相差异(χ2=25.165,p=0.001<0.05;χ2=3.955,p=0.047<0.05),其中原发性高血压组235T T基因型频率为57.69%,高于人群对照组,而174MT+MM基因型频率为14.10%,低于人群对照组26.83%;脑梗死组与人群对照组M235T多态性分布也有显著性差异(χ2=25.165,p=0.001<0.05),235T T基因型频率在脑梗死组为53.66%,高于人群对照组。而T174M多态性在脑梗死组与人群对照组之间分布无显著性差异。结论:M235T和T174M多态性与原发性高血压发生相关,M235T多态性与脑梗死发生相关。g     

5,10-亚甲基四氢叶酸还原酶基因多态性与脑梗死患者颈动脉粥样硬化的相关性研究

目的探讨血浆同型半胱氨酸(homocysteine,Hcy)代谢酶5,10-亚甲基四氢叶酸还原酶(5,10-methylenetetrahydrofolate reductase,MTHFR)C677T基因多态性与脑梗死患者颈动脉粥样硬化的相关性。方法纳入新发前循环大动脉粥样硬化性脑梗死组患者,以无脑梗死的门诊体检者作为对照组。用荧光偏振免疫法测定两组血浆Hcy水平,彩色多普勒超声进行双侧颈动脉颅外段检查明确是否存在动脉粥样硬化斑块及斑块性质,采用全自动基因芯片检测目标人群MTHFR C677T基因型。结果共纳入新发前循环脑梗死组患者150例,对照组100例。①脑梗死组MTHFR C677T突变(TT)基因型及T等位基因频率显著高于对照组(48.0%vs 19.0%,χ~2=22.067,P0.001;64.0%vs 45.5%,χ~2=6.907,P=0.009);②脑梗死组MTHFR C677T C→T基因突变与颈动脉粥样硬化狭窄程度呈正相关(r=0.353,P0.001);③脑梗死组中不稳定斑块组MTHFR C677T突变(TT)基因型及T等位基因频率显著高于稳定斑块组(66.2%vs 34.1%,χ~2=14.587,P0.001;77.5%vs 60.2%,χ~2=6.978,P=0.008)。结论 MTHFR C677T位点C→T基因突变是颈动脉粥样硬化斑块不稳定性及其狭窄程度的相关危险因素。     

Relationship between the -455G/A and -148C/T polymorphisms in the beta-fibrinogen gene and cerebral infarction in the Xinjiang Uygur and Han Chinese populations

We sought to investigate the correlation between the -455G/A and -148C/T polymorphisms of the β-fibrinogen gene and plasma fibrinogen levels in patients with cerebral infarction and in healthy subjects among the Xinjiang Uygur and Han Chinese populations, by using polymerase chain reaction-restriction enzyme digestion analysis. Results showed that there were no statistically significant differences in the distributions of the -455G/A genotype and allele frequency between the Uygurs and the Han. Plasma fibrinogen levels in cerebral infarction patients among the Uygurs and the Han were higher than those among healthy subjects. In particular, the frequencies of the -455G/A AA and -148C/T TT genotypes were significantly higher than in healthy subjects. Individuals carrying the A or T allele had a higher incidence of cerebral infarction compared with those carrying the G or C allele. Our experimental findings indicate that the -148C/T and -455G/A polymorphisms are associated with cerebral infarction in Xinjiang Uygur and Han Chinese subjects. The susceptibility- conferring alleles are -148T and -455A, and the susceptibility-conferring genotype is -455G/A + AA.     

Association of Single-Nucleotide Polymorphisms in the Cannabinoid Receptor 2 Gene with Schizophrenia in the Han Chinese Population

Cannabinoid receptor 2 (CNR2) is a major receptor in the endogenous cannabinoid system. In recent years, many studies have shown that the receptor is closely associated with schizophrenia. This study examined the relationship between CNR2 gene polymorphisms (rs2501432C/T, rs2229579C/T, rs2501401G/A) and schizophrenia. Three hundred sixteen schizophrenia patients and 334 healthy subjects were recruited as case and control groups, respectively. For rs2501432, the CT/TT genotype frequencies in the dominant model, TT genotype frequencies in the additive model, and T allele frequencies of the case group were lower than the control (P?<?0.05), and the CT and TT genotypes and T allele frequencies of the male case group were significantly lower than the control (P?<?0.05). For rs2229579, the T allele frequencies of the case group were higher than the control (P?<?0.05). The T-C-G haplotype in the case group had a significantly lower frequency compared with the controls, but the T-T-A haplotype frequencies were higher in the case group than in the controls (P?<?0.05). Our results suggest that the T allele of rs2501432 may be a protective factor, particularly in males, but the T allele of rs2229579 may be a risk factor for schizophrenia. T-C-G may be a protective haplotype for schizophrenia, but not the T-T-A haplotype.     

趋化因子受体CCR2b基因G190A多态性与脑梗死关系的研究

目的 探讨趋化因子受体CCR2b基因G190A多态性与中国福建地区汉族人群脑梗死(cerebral infarction,CI)的关系.方法 采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)和DNA序列测定法检测200例CI及200名健康对照者趋化因子受体CCR2b基因G190A多态性分布,对两组之间的基因型频率和等位基因频率进行比较.结果 CI组趋化因子受体CCR2b基因G190A多态位点的基因型和等位基因频率分布与对照组比较差异有统计学意义(P<0.05).脑梗死组GG、GA、AA基因型频率分别为83.5%、15.0%、1.5%;G、A等位基因频率分别为91.0%、9.0%.正常对照组GG、GA、AA基因型频率分别为73.0%、22.5%、4.5%;G、A等位基因频率分别为84.3%、15.7%.脑梗死组GG基因型和G等位基因频率高于对照组(P<0.05).结论 趋化因子受体CCR2b基因G190A多态性与脑梗死的发病具有相关性,G等位基因可能是中国福建地区汉族人群脑梗死发病的遗传易感基因.

Abstract：

Objective To investigate the relationship between chemokine receptor CCR2b gene G190A polymorphism and cerebral infarction(CI)of Han population in Chinese Fujian district.Methods The G190A polymorphism in ccr2b gene was detected by polymerase chain reaction-restriction fragment length polymorphism analysis(PCR-RFLP)and DNA sequencing in 200 patients with CI(CI group)and 200 normal controls(NC group).Results There were significant differences in frequencies of allele and genotype of CCR2b G190A gene polymorphism between CI and control groups(P<0.05).In CI group,genotypic frequency of GG Was 83.5%,GA wag 15.0%,AA Was 1.5%.The allele frequency of G Was 91.0%and A was 9.0%.In NC group,genotypic frequency of GG WaS 73.0%,GA was 22.5%,AA was 4.5%.The allele frequency of G was 84.3%and A was 15.7%.The frequencies of CCR2b 190GG genetype and G allele in CI group were siginificantly higher than that in NC group(P<0.05).Conclusions There was association between CCR2b gene G190A polymorphism and cerebral infarction(CI)in Chinese Fujian district Han populations.The CCR2b G190 allele may be a genetic risk factor for cerebral infarction of Hart populations in Chinese Fujian district.