C反应蛋白基因-390C/A/T多态性与冠心病的相关性

摘要

目的 探讨我国汉族人群中C反应蛋白(C reactive protein,CRP)基因启动子区-390C/A/T单核苷酸多态性的分布,及其与冠心病的相关性. 方法对冠心病组(111例)和对照组(101例)利用聚合酶链反应扩增出相应目的 条带,然后运用序列特异性的聚合酶链反应检测其多态性. 结果 -390C/A/T多态性的等位基因频率在冠心病组中C为64.4%(143/222),A为22.1%(49/222),T为13.5%(30/222);在对照组中,C为77.7%(157/202),A为14.9%(30/202),T为7.4%(15/202),差异有统计学意义(χ~2=29.30,P<0.01).基因型频率在冠心病组中CC为37.8%(42/111),CT为24.3%(27/111),CA为28.8%(32/111),TA为0.9%(1/111),TT为0.9%(1/111),AA为7.2%(8/111);在对照组中CC为60.4%(60/101),CT为11.9%(12/101),CA为22.8%(23/101),TA为1.0%(1/101),TT为1.0%(1/101),AA为3.0%(3/101),差异有统计学意义(χ~2=12.57,P<0.01).运用多元对数回归分析冠心病其他相关危险因素(体质指数、年龄、三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、血糖、糖尿病、吸烟、饮酒和高血压),排除其对CRP基因启动子区多态性的影响,发现该位点依然与冠心病相关,那些带有T等位基因个体患冠心病的概率是不带T等位基因个体的2.66倍(OR=2.66,95%CI 1.05～6.75,P<0.05).结论 -390C/A/T与冠心病相关,其T等位基因是冠心病的独立危险因素,该位点可能是潜在的冠心病基因诊断标记.%Objective To investigate the distribution of single nucleotide polymorphism (SNP) of -390C/A/T within C-reactive protein (CRP) gene promoter region in ethnic Han Chinese, and its association with coronary heart disease (CHD). Methods Altogether 111 CHD patients and 101 controls were enrolled in this study. The target fragments were amplified by PCR. Then the -390C/ A/T polymorphism was screened by Sequence Specific PCR (SSP). At last, the association was analyzed by proper statistical analysis. Results In CHD group, as to allele frequencies of -390C/ A/T polymorphism, C was 64.4%, A was 22.1% and T was 13.5%. And in control group, C was 77.7%, A was 14.9% and T was 7.4%. There were significant differences in the distribution between patients and controls (χ~2=29.30, P<0.01). In the genotyep frequencies of CHD group, CC was 37.8%, CT was 24.3%, CA was 28.8%, TA was 0.9%, TT was 0.9% and AA was 7.2%. In control group, CC was 60.4%, CT was 11.9%, CA was 22.8%, TA was 1.0%, TT was 1.0% and AA was 3.0 %; there were significant differences between these two groups (χ~2=12.57, P<0.01). After controlling other CHD risk factors by multivariate logistic regression analysis, the association between polymorphism and CHD remained. Individuals carrying the -390C/A/T allele had 2.66-fold higher risk for developing CHD (OR=2.66, 95% CI 1.05-6.75, P<0.05). Conclusions The -309C/A/T polymorphism is associated with CHD, and the T allele in this polymorphism may be an independent risk factor for CHD, it may be a potential genetic maker for CHD.