ALOX5 AP基因多态2354T/A和MTHFR基因多态677C/T的协同作用显著增加脑梗塞的易患性  

Polymorphisms of 2354T/A in the ALOX5AP Gene and 677C/T in the MTHFR Gene Synergistically Increase the Risk for Atherothrombotic Stroke in Men

作　　者：张伟丽[1] 石佳[1] 杨晓敏[1] 孙凯[1] 惠汝太 

机构地区：[1]中国医学科学院中国协和医科大学阜外心血管病医院中德分子生物学实验室,北京市100037

出　　处：《中国分子心脏病学杂志》2005年第1期395-400,共6页Molecular Cardiology of China

基　　金：国家973重点基础研究发展规划的资助项目(G200056901)

摘　　要：目的研究MTHFR多态性和编码5-脂氧合酶激活蛋白的基因ALOX5AP多态性,尤其是基因之间的相互作用,是否与脑卒中的易患性相关。方法采用PCR-RFLP方法,对来自7个临床中心的1823名对照和1832名脑卒中患者检测了基因ALOX5AP和MTFHFR的3个多态性,基因分型结果经测序进一步确证。多元logistic回归方法校正了传统危险因素后分析基因多态性与脑卒中的独立相关性。检测7个与脑卒中不相关的微卫星多态标记在病例-对照人群的频率分布以评估人群层化程度。结果MTHFR6771TT基因型与男性脑梗塞的发病风险呈弱相关(OR,1.45;95%CI:1.04-2.02;P=0.020),ALOX5AP2354AA基因型也增加男性脑梗塞1.55倍的发病风险(95%CI:1.03-2.35;PP:0.038)。当个体同时携带MTHFR677TT和ALOX5AP2354AA基因型时,男性脑梗塞的相对患病风险率显著增加至3.58倍((95%CI:1.72-7.43;P=0.001)。微卫星多态性标记的各主要等位基因片段的频率在病例和对照组无显著性差异。结论MTHFR677TT基因型和ALOX5AP2354AA基因型的协同作用与增加的男性脑梗塞患病风险呈显著相关。对于多因素复杂性疾病,综合分析弱效基因的相互作用有助于了解个体易患脑卒中的遗传背景。Objective Atherosclerosis is an inflammatory disease. Elevated plasma homocysteine and leukotrienes have been reported to induce and promote inflammation or atherosclerosis. In the present study, we assessed whether genetic variants in the ALOXSAP gene encoding 5-1ipoxygenase activating protein and the MTHFR gene which is responsible for homocysteine metabolism, would synergistically influence the risk of stroke. Methods A total of 1823 patients with stroke and 1832 controls were recruited from seven clinical centers. Polymorphisms 677C/T in the MTHFR gene and 2354T/A and 16699G/A in the ALOXSAP gene were genotyped by polymerase chain reaction and restriction enzyme analysis. Multivariate logistic regression model was used to exclude the influence of confounding factors and determine the interaction among polymorphisms on the risk of stroke. Results A weak association of MTHFR 677TT genotype with thrombotic stroke was identified （odds ratio-OR, 1.45; 95% confidence interval-CI, 1.04 to 2.02, P =0.020） only in men, so did the 2354AA genotype of ALOXSAP （ OR, 1.55 ; 95% CI, 1.03 to 2.35 ; P = 0.038 ）. When the two homozygous variants were combined, their risk for thrombotic stroke was markedly increased to 3.58 folds （ 95% CI, 1.72 to 7.43 ; P = 0. 001 ） in male patients. Conclusion The MTHFR 677TT and ALOXSAP 2354AA genotypes synergistically confer higher risk for thrombotic stroke in men.

关 键 词：亚甲基四氢叶酸还原酶 白三烯 遗传 危险因素 脑卒中 

分 类 号：R743.33[医药卫生—神经病学与精神病学]