凝血因子ⅡG20210A、ⅤG1691A及ⅦR353Q基因多态性与上海汉族人群急性脑梗死的相关性  

Association of Coagulation FactorsⅡG20210A,ⅤG1691A andⅦR353Q Gene Polymorphisms with Acute Cerebral Infarction among Han Population in Shanghai

作　　者：岳孟孟 于芳苹[2] 赵迎春[1] YUE Mengmeng;YU Fangping;ZHAO Yingchun(Department of Neurology,Shanghai Songjiang Clinical Medical College,Nanjing Medical University,Shanghai 201600,China;Department of Geriatrics,Shanghai Songjiang Clinical Medical College,Nanjing Medical University,Shanghai 201600,China)

机构地区：[1]南京医科大学上海松江临床医学院神经内科,上海201600 [2]南京医科大学上海松江临床医学院老年科,上海201600

出　　处：《贵州医科大学学报》2020年第7期797-804,共8页Journal of Guizhou Medical University

基　　金：上海市松江区科学技术攻关项目(2017sjkjgg46);江苏省研究生科研与实践创新计划项目(KYCX18-1506)。

摘　　要：目的:探讨凝血因子ⅡG 20210 A(FⅡG 20210 A)、ⅤG 1691 A(FⅤG 1691 A)及ⅦR 353 Q(FⅦ)基因多态性与上海汉族人群急性脑梗死(ACI)的相关性。方法:选取上海地区汉族ACI确诊患者180人作为ACI组[大动脉粥样硬化型(LAA,n=65)、小动脉硬化性或腔隙性(SAO,n=84)及心源性(CE,n=31)],同期健康体检的汉族人群150例作为对照组,收集2组研究对象的临床资料并比较;分别抽取2组研究对象入院或体检时清晨空腹外周血2 mL,采用聚合酶链式反应-限制性片段长度多态性(PCR-LDR)和多重连接酶检测(Multiple LDR)技术进行FⅡ、FⅤ、FⅦ基因分型检测并比较,采用活化蛋白C抵抗(APCR)试剂盒测定2组被检者外周血APCR阳性表达,采用Hardy-Weinberg平衡法检验样本的群体代表性,采用Logistic回归分析筛查ACI的危险因素。结果:ACI组与对照组研究对象的FⅡG 20210 A、FⅤG 1691 A及FⅦR 353 Q多态性符合Hardy-Weinberg平衡(P>0.05);FⅡG 20210 A的PCR产物经过HindⅢ酶切之后显示基因型为GG型(320 bp),Multi-LDR结果与PCR-RFLP结果一致,仅检测出GG基因型;FⅤG 1691 A的PCR产物经过MnlⅠ酶切显示基因型为GA型(353 bp、205 bp及148 bp)和GG型(205 bp和148 bp);ACI组及对照组被检者均未检测出AA纯合突变基因型;FⅦR 353 Q的PCR产物经过MspⅠ酶切结果显示基因型为RQ型(291 bp、223 bp和68 bp)、RR型(223 bp和68 bp)和QQ型(291 bp),Multi-LDR结果与PCR-RFLP结果一致;ACI组FⅦR 353 Q基因型频率和等位基因频率与对照组比较,差别有统计学意义(P<0.05);SAO组与对照组差异有统计学意义(P<0.05),ACI组APCR阳性率高于对照组(P<0.05);二分类Logistic回归分析结果显示,吸烟、高血压、低水平高密度脂蛋白、FⅦR 353 Q基因型及APCR是ACI的独立危险因素(P<0.05)。结论:FⅡG 20210 A及FⅤG 1691 A基因多态性在上海汉族ACI患者中较少见,FⅦR 353 Q基因多态性与上海汉族人群ACI有关,其中Q等位基因可能是保护性因素。Objective:To asses the association of coagulation factorsⅡG20210A(FⅡG20210A),ⅤG1691A(FⅤG1691A)andⅦR353Q(FⅦ)gene polymorphisms with acute cerebral infarction(ACI)among ethic Han in Shanghai.Methods:One hundred and eighty ethic Han patients diagnosed with ACI in Shanghai were selected as the ACI group,including aortic atherosclerosis(LAA,n=65),arteriosclerosis or lacunarity(SAO,n=84),and cardiogenicity(CE,n=31),and 150 healthy ethic Han persons in the same period as control group.Clinical data of study subjects were collected and compared.2 mL of fasting peripheral blood was collected in the early morning of the admission to our hospital or physical examination.Polymerase Chain reaction-restriction fragment length polymorphism(PCR-RFLP)and multiple ligase detection(Multiple LDR)assays were used to genotype FⅡ,FⅤ,FⅦ.Activated protein C resistance(APCR)kit was used to determine plasma APCR expression.The Hardy-Weinberg equilibrium was used to test the representativeness of the samples.Logistic regression analysis was used to screen risk factors for ACI.Results:The FⅡG20210A,FⅤG1691A and FⅦR353Q gene polymorphisms were in accordance with Hardy-Weinberg equilibrium(P>0.05).Agarose gel electrophoresis analysis showed that the PCR product of FⅡG20210A digested with HindⅢhad only GG type(320 bp),consistent with multi-LDR result.The PCR product of FⅤG1691A digested with Mnl I had GA type(353 bp,205 bp and 148 bp)and GG type(205 bp and 148 bp).AA type was not detected.The PCR product of FⅦR353Q digested with MspⅠhad RQ type(291 bp,223 bp and 68 bp),RR type(223 bp and 68 bp)and QQ type(291 bp),consistent with multi-LDR results.The genotype frequency and allele frequency of FⅦR353Q in ACI group were different from those in the control group(P<0.05),and the difference between the SAO group and the control group was statistically significant(P<0.05).The positive rate of APCR was higher in the ACI group than that in the control group(P<0.05).Binary logistic regression analysis showed that smok

关 键 词：血液凝固因子 活化蛋白C抵抗 急性脑梗死 基因多态性 凝血因子ⅡG 20210 A 凝血因子ⅤG 1691 A 凝血因子ⅦR 353 Q 

分 类 号：R743.3[医药卫生—神经病学与精神病学]