5-脂氧合酶激活蛋白基因多态性与环境因素在缺血性卒中发生中的交互作用

摘要

目的 探讨5-脂氧合酶激活蛋白基因(ALOX5AP基因)启动子区rs17222919位点基因多态性与环境因素在河南汉族人群缺血性卒中(IS)发病中的交互作用.方法 对河南省汉族622例IS患者和631名健康对照者进行环境危险因素调查,运用TaqMan-PCR技术对ALOX5AP基因rs17222919位点进行基因分型,探讨其与IS发生的相关性,并根据交互作用系数(Υ,Υ=βeg/βe)判断交互作用及其作用模型.结果 IS组rs17222919位点的TG(189/622,30.4％)、GG(18/622,2.9％)基因型频率及G等位基因频率(225/1244,18.1％)显著低于健康对照组(221/631,35.0％；31/631,4.9％;283/1262,22.4％),差异具有统计学意义(x2 =4.117,P=0.042;x2=4.457,P=0.035;x2 =7.294,P=0.007).TG+GG基因型与高血压、糖尿病、吸烟之间在IS发病中均存在负向交互作用(y =0.943、0.922、0.830),其作用模型均为超相乘模型.结论 IS的发生是遗传及环境因素相互作用的结果.在河南汉族人群中,rs17222919位点G等位基因可能对IS发病的环境危险因素高血压、糖尿病、吸烟暴露的效应具有减弱作用.%Objective To explore the interaction between polymorphisms of rs17222919 which located in the 5-1ipoxygenase-activating protein(ALOX5AP) gene promoter and environmental risk factors in ischemic stroke(IS).Methods We conducted a case-control study involving a total of 622 cases and 631 unrelated healthy controls which were selected from Henan Han populations,and the environment risk factors were recorded.Genotyping aimed at detecting both genetic and environmental factors in relation to IS was performed by TaqMan-polymerase chain reaction technology while interaction indexes (Υ) were calculated to determine interactions and their role models.Results The rs17222919 TG (189/622,30.4％),GG (18/622,2.9％)genotype frequencies and G (225/1244,18.1％)allele frequencies in IS subjects were significantly lower than those in controls (221/631,35.0％ ; 31/631,4.9％ ; 283/1262,22.4％ ; x2 =4.117,P =0.042 ; x2 =4.457,P =0.035 ; x2 =7.294,P =0.007).Negative interactions between TG + GG genotype and hypertension,diabetes or cigarette smoking in the occurrence of IS (Υ =0.943,0.922,0.830) were observed,whose role models were all super-multiplicative models.Conclusions According to our study,ischemic stroke is the result of the interaction of genetic and environmental factors and G allele of rs17222919 may have weakened the role of environmental factors for hypertension,diabetes and cigarette smoking in IS incidence.