脂蛋白脂酶Ser447Stop基因多态与脑梗死的相关性

目的 探讨脂蛋白脂酶(LPL)Ser447Stop基因多态与脑梗死的相关性.方法 受试者共883人,其中脑梗死组563例[包括动脉粥样硬化(AS)性脑梗死329例和腔隙性脑梗死234例],对照组320名,应用聚合酶链反应一限制性片段长度多态性方法,对LPL基因Ser447Stop位点进行基因多态性检测.结果 脑梗死组、AS性脑梗死组和腔隙性脑梗死组LPL Ser447Stop GG+CG基因型频率与对照组相比,差异无统计学意义,AS性脑梗死组G变异等位基因频率(64例,9.7%)与对照组(42例,6.6%)相比差异有统计学意义(X2=3.99,P=0.045).相对于C等位基因,G等位基因的彻值为1.510(95%C/1.012～2.261).结论 LPL Ser447Stop G变异等位基因携带者患AS性脑梗死的危险高于非携带者.G变异等位基因可能是AS性脑梗死高危险性的遗传标志之一.     

脂蛋白脂酶基因Ser447stop多态性与脑出血的关系

目的探讨脑出血与脂蛋白脂酶基因Ser447stop多态性相关性。方法采用聚合酶链反应和限制性片段长度多态性方法(PCR-RFLP法)来检测脂蛋白脂酶基因Ser447stop多态性,其中对照者66例,脑出血患者69例,测定所有样本的血脂水平。结果1、脑出血患者组CG基因型和G等位基因频率显著低于对照组(P<0.05);2、脑出血患者组血清TG、LDL-c水平较对照组高(P<0.01);同时CHO、ApoAⅠ、ApoB水平降低(P<0.01);3、CC基因型LDL-c含量较CG型高(P<0.05)。结论脂蛋白脂酶基因Ser447stop多态性与脑出血有一定关联,G等位基因可能是脑出血的一种保护性因素。     

脂蛋白脂酶Ser447Term多态性和卒中相关危险因素相互作用对缺血性脑卒中发病的影响

目的 本研究旨在探讨脂蛋白脂酶(LPL) Ser447Term多态性与一些常见的卒中危险因素之间的相互影响.方法 检测704个汉族缺血性脑卒中患者的基因型,根据这些患者所具有的卒中相关危险因素将其分为2型糖尿病组、高血压组、吸烟组和高脂血症组.应用聚合酶链反应-限制性片段长度多态性方法对Ser447Term的多态性进行基因分型.结果 卡方(x2)检验结果显示:在有糖尿病史的卒中患者中Ser447Term G等位基因的携带率显著高于无糖尿病史的卒中患者(x2=7.25,P=0.007,OR=1.78,95％ C/I.18～ 2.68).这样的相关性并未在具有其他3个卒中相关的危险因素的患者中观察到.结论 LPL基因多态性与糖尿病的联合作用可能促成缺血性卒中的一个亚组的发病.     

RAGE基因Gly82Ser多态性与脑梗死的相关性研究

目的针对脑梗死多因素致病的特点,探讨RAGE基因Gly82Ser多态性与糖尿病合并脑梗死、高血压合并脑梗死和单纯脑梗死的关系。方法应用聚合酶链反应-限制性片段多态性(PCR-RLFP)的方法检测糖尿病合并脑梗死56例,高血压合并脑梗死60例,单纯性脑梗死46例,健康人对照50例汉族人RAGE基因Gly82Ser外显子3内82位点基因型频率和等位基因频率。结果高血压合并脑梗死组病人RAGE基因杂合子基因型(GS)频率明显高于对照组(P<0.05),其等位基因(G,S)频率与对照组比较无差异(P>0.05);糖尿病合并脑梗死组和单纯脑梗死组基因型(GG,GS,SS)和等位基因(G,S)与对照组比较无统计学差异(P>0.05)。结论高血压合并脑梗死病人RAGE基因Gly82Ser杂合子基因型(GS)增多,可能是高血压合并脑梗死病人的危险因素;RAGE基因Gly82Ser的多态性与糖尿病合并脑梗死和单纯脑梗塞病人发病、发展无关。     

NADPH氧化酶p22~(phox)亚基基因多态性与急性动脉硬化性脑梗死的关联性研究

目的探讨CYBA基因的多态性位点与急性动脉硬化性脑梗死的相关性。方法收集284例脑梗死患者(脑梗死组)及335例同期健康体检者(对照组),采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测CYBA基因rs4673和rs3180279位点的基因型。结果 rs4673位点的基因型及等位基因频率分布在脑梗死组和对照组中差异无统计学意义(P0.05)。脑卒中组男性患者rs3180279位点GC、GG基因型的频率低于对照组,CC基因型的频率高于对照组(P=0.034)。结论 CYBA基因的rs4673位点与中国北方汉族人群的急性动脉硬化性脑梗死无相关性,男性rs3180279位点GG+GC基因型的携带者较CC基因型携带者动脉硬化性脑梗死的发病率可能更低。     

RAGE基因多态性与高血压左室肥厚、血清esRAGE水平的相关性研究

目的探讨晚期糖基化终末产物受体(RAGE)基因Gly82Ser多态性与EH-LVH患者及其血清内源性分泌型RAGE(esRAGE)水平的相关性。方法应用聚合酶链反应-限制性片段多态性(PCR-RLFP)的方法,检测94例EH患者(其中38例伴LVH)及50例对照组RAGE基因Gly82Ser多态性,同时采用ELISA法测定血清esRAGE水平。结果与正常对照组相比,EH组基因型频率和等位基因频率差异无统计学意义(P>0.05);EH-LVH组RAGE基因Gly82Ser位点的GS基因型频率和82Ser等位基因频率明显增高,差异有统计学意义(P<0.05);EH-LVH和EH组Gly82Ser SS基因型血清es-RAGE水平与对照组相比差异显著(P<0.05)。结论 RAGE基因Gly82Ser多态性与EH的发生发展无关;EH-LVH患者RAGE基因Gly82Ser GS基因型和82Ser等位基因增多,提示82Ser等位基因可能是EH-LVH发病的易感基因;RAGE基因Gly82Ser多态性与血清esRAGE水平显著相关。     

单核细胞趋化蛋白-1基因-2518G/A多态性与中国湖南地区汉族人群脑梗死关系的研究

目的探讨单核细胞趋化蛋白-1(MCP-1)基因-2518G/A多态性与中国湖南地区汉族人群脑梗死(CI)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)、DNA测序等方法检测162例CI患者(CI组)和150名健康对照者(NC组)MCP-1基因-2518G/A多态性;采用酶联免疫吸附试验(ELISA)检测两组血清MCP-1水平。结果CI组GG、GA、AA基因型频率分别为39.5%、37.0%、23.5%,G、A等位基因频率分别为58.0%、42.0%;NC组GG、GA、AA基因型频率分别为27.3%、39.3%、33.4%,G、A等位基因频率分别为47.0%、53.0%。CI组GG基因型和G等位基因频率显著高于NC组(均P<0.05)。CI组血清MCP-1含量[(157.68±11.60)pg/ml]明显高于NC组[(131.82±10.72)pg/ml](P<0.05);MCP-1基因-2518G/A多态位点中含G等位基因者(GG+GA)血清MCP-1含量[(149.44±15.71)pg/ml]显著高于非G等位基因携带者(AA)[(134.57±15.84)pg/ml](P<0.05)。结论MCP-1基因-2518G/A位点的G等位基因可能是中国湖南地区汉族人群CI发病的遗传易感基因。携带G等位基因的个体可能通过上调MCP-1表达而增加CI的发病风险。     

CCR2b基因190G/A多态性与脑出血的相关性研究

目的探讨趋化因子受体CCR2b基因190G/A多态性与中国湖南地区汉族人群脑出血(ICH)的关系。方法应用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)技术检测158例脑出血患者和150名年龄、性别相匹配的正常对照者趋化因子受体CCR2b基因190G/A的基因型分布及等位基因频率,比较不同群体的表型差异及其对脑出血的影响。结果中国湖南汉族人群存在趋化因子受体CCR2b基因190G/A多态性,趋化因子受体CCR2b 190G/A基因型分布为AA 3.6%,GA 22.1%和GG 74.3%,等位基因A和G频率分别0.146和0.854。在对照组中,趋化因子受体CCR2 b 190 G/A基因型分布为AA 5.3%,GA 28.0%和GG 66.7%,等位基因A和G频率分别0.193和0.807。在脑出血组中,趋化因子受体CCR2b 190G/A基因型分布为AA 1.9%,GA 16.5%和GG 81.6%,等位基因A和G频率分别0.102和0.898。脑出血组趋化因子受体CCR2 b基因190 G/A多态位点的A等位基因频率显著低于对照组(P<0.05),这种差异在合并高血压和冠心病患者中尤为明显。应用Logistic回归校正了脑出血的环境危险因素后,CCR2b190A仍可使脑出血发生的危险性降低(OR=0.205,95%CI:0.092～0.454,P=0.000)。结论 CCR2b基因190G/A位点的A等位基因可能是湖南地区汉族人群脑出血的一种保护性基因多态。     

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.     

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。     

脂蛋白相关磷脂酶A2基因A379V多态性与TOAST亚型的关系

目的探讨脂蛋白相关磷脂酶A2(lipoprotein associated phospholipase A2,Lp-PLA2)血清水平及其基因A379V多态性与低分子肝素实验病因分型(the trial of Org 10172 in acute stroke treatment,TOAST)的关系。方法对急性期脑梗死患者(N=200)和对照组(体检中心健康体检者,N=172)应用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清Lp-PLA2水平,聚合酶链反应(polymerasechain reaction,PCR)及基因测序技术检测基因多态性。结果脑梗死组血清Lp-PLA2水平(24.39±6.63)ng/ml,高于对照组(15.78±4.32)ng/ml,差异有显著性(P<0.01);TOAST分型后比较,大动脉粥样硬化性梗死(large artery atherosclerotic stroke,LAA)组、小动脉闭塞性梗死(small artery occlusion stroke,SAO)组、对照组血清Lp-PLA2水平分别是(25.60±6.71)ng/ml、(21.43±5.47)ng/ml、(15.78±4.32)ng/ml,差异有显著性(P<0.01);脑梗死组惠者,Lp-PLA2基因A379V多态性位点CC基因型频率68%,C等位基因频率83%,与对照组的70.9%、84.3%比较,差异无显著性(P>0.05),但是TOAST分型后显示CC纯合子血清Lp-PLA2水平(26.27±6.25)ng/ml较T等位基因携带者(CT+TT)(20.39±5.64)ng/ml发生脑梗死的风险增加(P<0.01)。结论 Lp-PLA2血清水平在脑梗死组升高,LAA组升高最明显;A379V基因多态性CC基因型与脑梗死的发病可能相关。     

脑出血患者屏氧酶1基因192位Gln-Arg多态性的研究

目的　探讨屏氧酶 1( PON1)基因 192位 Gln- Arg( Q/ R192 )多态性与脑出血关系。方法　应用聚合酶链式反应 -限制性片段长度多态性 ( PCR- RFL P)方法 ,对 30 5例脑出血患者和 339例正常对照者 PON1Q/ R192基因多态性进行研究。结果　在脑出血组中 ,PON1Q/ R192 3种基因型频率分别为 QQ13.1%、QR4 8.2 %、RR38.7%。PON1Q/ R192基因型和等位基因频率分布在脑出血组与对照组之间无显著性差异 ( P>0 .0 5 ) ;各基因型之间血脂水平无显著性差异 ( P>0 .0 5 )。结论　研究未发现 PON1Q/ R192基因多态性与脑出血存在相关关系     

Lipoprotein lipase Ser447Ter polymorphism associated with the risk of ischemic stroke: a meta-analysis

Introduction

Previous studies suggested lipoprotein lipase (LPL) Ser447Ter and Asn291Ser polymorphisms were associated with the risk of ischemic heart disease, however, their effects on ischemic stroke were controversial. A meta-analysis was performed to assess the associations between these two LPL polymorphisms and the risk of ischemic stroke.

Methods

The electronic databases PubMed and Embase were used to identify relevant studies by two interviews independently. The pooled odds ratios (ORs) and weighted mean differences (WMD) with 95% confidence interval (CI) were estimated for the risk of ischemic stroke and the plasma lipids in various Ser447Ter genotypes respectively. A fixed or random effect model was selected for pooling data based on homogeneity test.

Results

13 studies including 4,681 ischemic stroke cases and 8,516 controls were involved in this meta-analysis. Overall, LPL Ter447 variant was associated with a significantly reduced risk for ischemic stroke (OR = 0.79, 95% CI: 0.68-0.93) both in Caucasian (OR = 0.87, 95% CI: 0.77-0.97) and East-Asian (OR = 0.65, 95% CI: 0.43-0.99), whereas no significant association of Ser291 variant was observed (OR = 1.25, 95% CI: 0.96-1.63). The Ser447Ter polymorphism may be more important in association with the decreased risk of atherosclerotic stroke (OR = 0.44, 95% CI: 0.32-0.62) which derived from significantly increased high density lipoprotein cholesterol, decreased triglyceride and total cholesterol in Ter447 carriers compared with non-carriers.

Conclusions

This meta-analysis indicated that LPL Ser447Ter polymorphism was associated with a significant reduction in the risk of ischemic stroke, especially atherosclerotic stroke subtype in both Caucasian and East-Asian.     

载脂蛋白A5-1131T>C基因多态性与脑卒中的关系

目的 探讨载脂蛋白(Apo)A5-1131T>C基因多态性与脑卒中的关系. 方法 对327例脑卒中患者(其中脑梗死患者194例,脑出血患者133例)及311名健康对照者的ApoA5-1131T>C基因多态性及血脂水平进行检测. 结果 脑梗死患者的-1131C等位基因频率明显高于对照者,差异有统计学意义(P<0.05);脑出血患者与对照者比较,差异没有统计学意义(p>0.05).在脑卒中患者中,C等位基因携带者的甘油三酯(TG)水平明显高于非C携带者.差异有统计学意义(p<0.05),总胆固醇(TC)、高密度蛋白胆固醇(HDDC)和低密度脂蛋白胆固醇(LDL-C)比较差异无统计学意义(p>0.05).LOgistic回归单变量分析显示TC+CC基因型与脑梗死风险增加相关,与脑出血无关;校正体重指数(BMD、高血压、糖尿病和HDL-C等相关因素的影响后.C等位基因仍显示为脑梗死的独立危险因素(OR=1.932,95%CI为1.057-3.532,P=0.032).结论 脑梗死患者ApoA5-1131C等位基因携带率明显高于对照者,ApoA5-1131T>C基因多态性对血清TG水平有影响.ApoA5-1131T>C基因变异可能增加缺血性脑卒中的易感性.     

趋化因子CXCL16基因A181V多态性与TOAST分型的相关性研究

目的 探讨趋化因子CXC配体16（chemokine CXC ligand 16,CXCL16）基因A181V位点多态性与血清CXCL16水平、脑梗死（cerebral infarction,CI）及急性卒中治疗低分子肝素试验病因分型法（the Trial of Org 10172 in Acute Stroke Treatment,TOAST）分型的关系。方法 采用聚合酶链反应-限制性片段长度多态性方法（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP）检测基因型,同时对脑梗死急性期患者（n=177）和对照组（查体中心老年健康查体者,n=74）应用酶联免疫吸附法（enzyme linked immunosorbent assay,ELISA）检测血清CXCL16水平。结果 CI组血清CXCL16水平明显高于对照组（P<0.001）;按TOAST分型后比较,大动脉粥样硬化性卒中（large artery atherosclerotic stroke,LAA）组、小动脉闭塞性卒中（small artery occlusion stroke,SAO）组及对照组三组之间血清CXCL16水平差异仍有显著统计学意义（P<0.001）;Logistic回归显示血清CXCL16水平是CI的独立危险因素（P<0.001）。CXCL16基因A181V多态性位点基因型频率及等位基因频率在CI组和对照组之间无显著差异（P>0.05）,但是TOAST分型后显示AA纯合子比G等位基因携带者（GA+GG）发生大动脉粥样硬化性卒中的危险增加（P<0.001）。多元线性回归显示,CXCL16基因A181V多态性与血清CXCL16水平独立相关（P=0.009）。结论 CXCL16基因A181V多态性与血清CXCL16水平有关,AA基因型与大动脉粥样硬化性卒中密切相关,A等位基因是大动脉粥样硬化严重程度的重要标志。     

Susceptibility gene for stroke or cerebral infarction in the Han population in Hunan Province of China

The scavenger receptor class B type I gene can protect against atherosclerosis; a mononucleotide polymorphism is associated with differences in blood lipid metabolism, postprandial serum lipid levels, insulin resistance, coronary artery disease and familial hyperlipidemia. In this study, the scavenger receptor class B type I gene exon 1 G4A gene polymorphism in atherosclerotic cerebral infarction patients, cerebral hemorrhage patients and normal controls was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The results showed that the GA + AA genotype frequency of scavenger receptor class B type I gene G4A in atherosclerotic cerebral infarction patients was similar to that in cerebral hemorrhage patients and normal controls; however, the A allele frequency was significantly lower than that in normal controls. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum level of low-density lipoprotein cholesterol was significantly lower than that in patients with the GG genotype, in both the atherosclerotic cerebral infarction and cerebral hemorrhage groups. The serum level of high-density lipoprotein cholesterol in patients with the scavenger receptor class B type I gene G4A GA + AA genotype was significantly higher, while the serum levels of low-density lipoprotein cholesterol and total cholesterol were significantly lower than those in normal controls with the GG genotype. Our experimental results suggest that the G4A polymorphism of the scavenger receptor class B type I gene is a possible predisposing risk factor for atherosclerotic cerebral infarction, and that it has no association with cerebral hemorrhage in the Han population in Hunan province of China. The A allele is possibly associated with the metabolism of high-density and low-density lipoprotein cholesterol.     

Genetic polymorphisms of low density lipoprotein receptor can modify stroke presentation

Abstract

Low density lipoprotein is transcytosed across the blood–brain barrier mediated by low density lipoprotein receptor (LDLR). LDLR in the brain is mainly expressed on capillary endothelial cells and is therefore considered to be an important susceptibility gene in modifying the stroke presentation. A HapMap-based haplotype-tagging single nucleotide polymorphism association study was conducted in an isolated Taiwanese population. Two hundred and ninety-two unrelated patients with cerebral infarction, 76 patients with small vessel occlusion (SVO) disorder and 216 with non-SVO disorder were enrolled. For rs2738446, under the dominant model, the odds ratios (ORs) associated with the CC genotype were computed, with GG + CG carriers considered as the reference group. Homozygote CC carriers had a two-fold increased risk of SVO disorder [OR=2·0, 95% confidence interval (CI)=1·08–3.70, p=0·025). For rs2738450, under the dominant model, the ORs associated with the CC genotype were computed, with AA + AC carriers considered as the reference group. Homozygote CC carriers had a 1·85-fold increased risk of SVO disorder (OR=1·85, 95% CI=1·01–3.33, p=0·04). When analysing the association between the haplotype related to rs2738446 and rs2738450 and SVO disorder, the most common haplotype allele CC was used as the reference, and the GA haplotype allele was associated with a 48% decreased risk of SVO disorder (OR=0·52; 95% CI=0·29–0.93, p=0·029). Haplotype-based analysis of LDLR in Taiwanese patients with cerebral infarction provided preliminary evidence suggesting that genetic polymorphisms of LDLR can modify the stroke presentation.     

5-羟色胺1Dβ受体基因861G／C多态性与强迫症关联的病例对照研究

目的：探讨5-羟色胺lDr3受体（5-HTRlDβ）基因861G／C多态性与强迫症的关联性。方法：对239例强迫症（强迫症组）患者和337名健康对照（对照组）通过聚合酶链式反应与限制性片段长度多态性基因分型技术对5-HTRlDB基因单核苷酸多态性位点861G／C进行基因分型。结果：861G／C位点基因型频率分布两组问比较差异有统计学意义（X2=7．59,df=2,P=0．023）,而等位基因频率分布差异无统计学意义;杂合子GC基因型与纯合子（GG＋CC）基因型（X。=4．59,P=0．03,OR=1．44,95％CI：1．03～2．01）或CC基因型与GG＋GC基因型（X2=6．85,P=0．009,OR：0．58,95％C1=0．38～0．87）两组间比较差异有统计学意义,而GG基因型与GC＋CC基因型差异无统计学意义。两组女性之间比较,基因型（）f。=11．98,df=2,P：0．0025）与等位基L天J频率（X。=4．90,af=1,P=0．03,OR=1．51,95％C1=1．05～2．17）分布差异有统计学意义,而两组男性之间比较,基因型与等位基因频率分布差异无统计学意义。,强迫症晚发（〉16岁）组与对照组基因型频率分布差异有统计学意义（×。=6．45,妙=2,P=0．04）,而等位基因频率分布差异无统计学意义;强迫症早发（≤16岁）组、强迫症临床3个亚组基因型与等位基因频率分布上与对照组之间差异均无统计学意义。结论：5-HTR1Dβ861G／C多态性可能与强迫症和晚发型强迫症仔在关联;G等位基因可能是女性强迫症的风险因子。