Toll样受体-4基因启动子区多态性与急性心肌梗死发病风险的关系

Relationship of promoter polymorphisms of Toll-like receptor 4 with risk of acute myocardial infarction

目的探讨Toll样受体-4(TLR4)基因多态性与急性心肌梗死(AMI)发病风险的关系。方法选取AMI患者244例(AMI组)和非AMI患者284例(对照组),采用聚合酶链反应-限制性片段长度多态性技术检测两组TLR4基因启动子区多态性(rs10116253和rs10983755),比较两组TLR4启动子区多态性的基因型分布差异,采用多因素Logistic回归模型分析TLR4基因启动子区多态性与AMI发病风险的关系。结果TLR4基因rs10116253、rs10983755均符合Hardy-Weiberg平衡。TLR4启动子区rs10116253和rs10983755多态性与AMI的总体发病风险无关(P均>0.05)。对于TLR4基因rs10116253多态位点,男性TC突变杂合型携带者AMI的发病风险是TT野生纯合型携带者的0.50倍,TC+CC突变型携带者AMI发病风险是TT野生纯合型携带者的0.51倍,伴有高血脂的TC杂合型携带者AMI发病风险是TT野生纯合型携带者的0.42倍,TC+CC突变型携带者AMI发病风险是TT野生纯合型携带者的0.46倍,差异均有统计学意义(P均<0.05)。TLR4基因rs10983755多态位点在性别、年龄、有无高血压、有无糖尿病及有无血脂异常等分层分析中均未见统计学差异(P均>0.05)。结论TLR4基因启动子区rs10116253多态性与AMI分层发病风险存在关系;rs10116253突变基因型可以降低男性人群、伴有高血脂人群AMI的发病风险。

Objective To investigate the association between the promoter polymorphisms of Toll-like receptor 4（ TLR4） and the risk of acute myocardial infarction（ AMI） in Northern Chinese Han population. Methods Two hundred and forty-four patients with AMI（ AMI group） and 284 patients without AMI（ control group） were enrolled in this study.Polymerase chain reaction restriction fragment length polymorphism was performed to detect the promoter polymorphisms of TLR4（ rs10116253 and rs10983755）. The distributions of genotypes were evaluated by Chi-square（ χ2） test. The association between each SNP and CAD risk was determined using multiple logistic regression analysis. Results The distributions of TLR4 rs10116253 and rs10983755 were in Hardy-Weinberg equilibrium. The TLR4 rs10116253 and rs10983755 polymorphisms were not associated with the total risk of AMI（ all P〈0. 05）. Compared with those carriers with wild TT genotype,male carriers with variant TC genotype had a 50% lower AMI risk. Compared with the male carriers with wild TT genotype,male carriers with variant genotype（ TC ＋ CC） had lower AMI risk by 0. 51 fold. Compared with the hyperlipidemic patients with the wild TT genotype,the patients with the TC variant genotype had lower AMI risk by 0. 42 fold. In comparison with the hyperlipidemic patients with wild TT genotype,the patients with variant genotype（ TC ＋ CC） had lower AMI risk by 0. 46 fold. Significant difference was found between them（ all P〈0. 05）. However,TLR4 rs10983755 polymorphism showed no statistical significance in the stratification analysis including sex,age,with or without hypertension,with or without diabetes mellitus and with or without dyslipidemia（ all P〉0. 05）. Conclusion Our results reveal an association between the promoter polymorphism rs10116253 of TLR4 and AMI risk. The variant genotype of TLR4rs10116253 can reduce the risk of AMI in male subjects or subjects with hyperlipidemia.