血管紧张素转换酶基因多态性与冠心病发病的关系及其机制

Correlation of angiotensin-converting enzyme gene I/D polymorphism with coronary heart disease and the pathogenesis

目的 :探讨血管紧张素转换酶 ( ACE)基因 16号内含子插入 ( I) /缺失 ( D)多态性与冠心病 ( CHD)发病的关系及其致病机制。方法 :运用 PCR技术检测 5 1例 CHD和 3 0例对照者 ACE基因 I/ D多态性频率 ,采用免疫化学方法测定血浆中假血友病因子 ( VWF)、D-二聚体、血小板 α颗粒膜蛋白 - 14 0 ( GMP- 14 0 )水平以及凝血酶和抗凝酶 ( AT- )的活性。统计受检者 CHD常规危险因子的情况及心功能分级水平。结果 :CHD组 DD基因型频率显著高于对照组 ( P <0 .0 5 ) ,心功能 ～ 级的 CHD患者 DD基因型频率 ( 0 .4 2 1)显著高于心功能 ～ 级患者 ( 0 .15 6) ( P <0 .0 5 ) ,且 D等位基因频率分布显著高于后者 ( P <0 .0 5 )。 CHD的常规危险因子及血浆中反映内皮受损和凝血纤溶功能改变的分子标记物水平在 ACE 3种基因型间差异均无显著性意义 ( P >0 .0 5 )。结论 :ACE基因多态性是 CHD的一个新的独立遗传危险因子 ,DD基因型可能是 CHD患者心功能不良的一个预后标记 。

Objective:This study was designed to investigate the correlation of insertion/deletion polymorphism in intron 16 of the ACE gene with the risk of coronary heart disease (CHD) as well as the pathogenesis.Method:We identified the ACE I/D genotype by PCR technique in 51 CHD patients and 30 CHD free subjects.The plasma VWF, D dimer, GMP 140 concentrations and activities of thrombin and AT Ⅲ were also measured by using immunochemical methods.Data of classical risk factors for atherosclerosis and classfication for cardiac function were acquired in all the study subjects.Result:The DD genotype of ACE gene was significantly higher in CHD group than in control group (P< 0.05 ).The frequencies of D allele and DD genotype were higher in CHD subjects with Ⅲ～Ⅳ grade cardiac function ( 0.421 ) than in CHD subjects with Ⅰ～Ⅱ grade cardiac function ( 0.156 )(P< 0.05 ).Classical risk factors for atherosclerosis as well as the marker of endothelium damage and coagulation fibrinolysis system dysfunction did not differ significantly among the three genotypes of ACE gene (P> 0.05 ).Conclusion:I/D polymorphism of ACE gene is a new independent genetic risk factor for CHD.The DD genotype of ACE gene might be an important prognostic marker for cardiac function in CHD patients.Its influence on coagulation fibrinolysis system and the pathogenesis needs further investigation.