G蛋白β3亚单位基因和α-内收蛋白基因多态性与早发冠心病的相关性研究

The association between G-protein β3 subunit and α-adducin polymorphisms and premature coronary heart disease

目的 观察G蛋白β3亚单位基因(GNB3)C825T和α-内收蛋白基因(ADD1)CA60W多态性在中国早发冠心病(coronary heart disease,CHD)患者中的分布情况及特点,探讨CHD发生的遗传学机制。方法 采用聚合酶链反应和限制性片段内切酶的方法检测了342例早发CHD患者(冠状动脉造影证实,其中男性275例,年龄<55岁,女性67例,年龄<65岁)及133例对照(冠状动脉造影阴性)的GNB3基因C825T和ADDl基因G460W多态性。结果 GNB3基因C825T多态性在两组人群中的分布差异有显著性,CHD组T等位基因和TT基因型频率显著高于对照组(P<0.05),ADD1基因CA60W的等位基因和基因型频率两组比较差异均无显著性(P>0.05)。Logistic回归分析结果显示:在调整了其他危险因素后,T等位基因携带者和具有TT基因型者早发CHD的相对危险度增加(T等位基因:OR=1.8,95％CI为1.117～3.040,P=0.017;TT 基因型:OR=2.4,95％CI为1.312～4.254,P=0.004)。进一步的联合基因型分析显示:同时具有GNB3 825TF基因型和ADD1 460WW基因型者比单独有825TT基因型者有较高的早发CHD的危险(OR=6.1;95％CI 1.316～27.945,P=0.021)。结论 GNB3基因C825T多态性的825T等位基因和TT基因型可能是CHD早期发病的遗传因素之一。在早发CHD患者中GNB3 825TT基因型和ADD1

Objective To assess whether G-protein 03 ( GNB3) subunit C825T and α-adducin (ADD1) G460W polymorphisms are associated with angiographically documented premature coronary heart disease (CHD) and discuss the genetic mechanism of the pathogenesis of CHD. Methods The genotypes were determined with polymerase chain reaction and allele-specific restriction enzyme analysis. Angiographically documented CHD patients (n = 342) and sex- and age- matched controls (re = 133) with negative coronary angiography were included in this study. Results The frequency of the GNB3 825TT genotype (26. 6 vs. 15. 0) and 825T allele (50. 7 vs. 41. 1) were significantly higher in the CHD group than that in the controls (P < 0. 05 - 0. 001). The frequency of the ADD1 G460W allele and genotypes were not significantly different in both groups (P > 0.05). The GNB3 825T allele carriers and 825TT genotype were associated with premature CHD (OR for TT, 2. 4; 95% CI 1. 312 - 4. 254; P = 0. 004; OR for T allele carries, 1.8; 95% CI 1. 117-3.040; P=0.017). Combined genotype analysis showed that individual with both GNB3 825TT genotype and ADD1 460WW genotype had a higher risk ( OR: 6. 1, 95% CI 1. 316 -27. 945, P =0. 021) than those with 825TT genotype along for premature CHD. Conclusions The GNB3 C825T polymorphism is significantly associated with premature CHD. Our data also suggest a significant interaction between the GNB3 825TT and the ADD1 460WW genotype in premature CHD.