胆固醇酯转运蛋白基因6个多态位点与冠心病的关系

目的:了解胆固醇酯转运蛋白(CETP)基因TaqIB等6种突变的多态性与海南汉族冠心病(CHD)的关系.方法:应用针对CETP基因TaqIB、I405V、D442G、R451Q、A373P和I14A多态位点设计的等位基因特异性PCR技术,对301例海南汉族正常对照组、334例海南汉族CHD患者中CETP基因多态位点进行了检测,统计各基因型频率,计算各等位基因频率.结果:①正常对照组和CHD组中,TaqIB多态位点均可检测出B_1B_1、B_1B_2、B_2B_2 3种基因型.正常对照组B_1B_1、B_1B_2、B_2B_2 3种基因型的频率分布为45.18%、39.87%、14.95%,B_1和B_2的等位基因频率分布为65.12%、34.88%;CHD组B_1B_1、B_1B_2、B_2B_2 3种基因型的频率分布为51.50%、31.74%、16.77%,B_1和B_2的等位基因频率分布为67.37%、32.63%.②I405V突变位点可检测出Ⅱ、Ⅳ、VV 3种基因型.正常对照组Ⅱ、Ⅳ、VV 3种基因型的频率分布为15.95%、48.50%、35.55%,Ⅰ和Ⅴ的等位基因频率分布为40.20%、59.80%; CHD组Ⅱ、Ⅳ、VV 3种基因型的频率分布为15.27%、35.33%、49.40%,Ⅰ和Ⅴ的等位基因频率分布为32.93%、67.07%.③D442G突变位点可检测出DD、DG 2种基因型.正常对照组DD、DG 2种基因型的频率分布为95.35%、4.65%,D和G的等位基因频率分布为97.67%、2.33%;CHD组DD、DG 2种基因型的频率分布为63.47%、36.53%,D和G的等位基因频率分布为81.74%、18.26%.④正常对照组和CHD组中均未检测到R451Q、A373P和I14A 3种突变类型.⑤正常对照组与CHD组I405V和D442G 2个多态位点的基因型分布和等位基因频率的比较差异有统计学意义,其余多态位点在正常对照组与CHD组之间差异均无统计学意义.结论:I405V和D442G的多态性与海南汉族CHD显著相关.I405V多态位点V等位基因、D442G多态位点G等位基因是海南汉族CHD的易感基因,而I405V多态位点I等位基因对其有保护作用.D442G多态位点DG基因型可使海南汉族人群CHD的发病危险性显著增加.

Study of correlations between six polymorphic loci of cholesterol ester transfer protein gene and coronary heart disease

Objective:To explore the correlation between the polymorphism of cholesterol ester transfer protein (CETP ) gene at six mutation loci, TaqIB, I405V, D442G, R451Q, A373P and I14A, and coronary heart disease (CHD) of Han ethnic in Hainan province. Method:The six polymorphic loci of CETP gene was probed with an allele specific-PCR (AS-PCR) in 301 healthy controls and 334 CHD patients of Han ethnic in Hainan province. The frequencies of the six genetic loci were calculated and compared. Result:The TaqIB locus was detected in B_1B_1,B_1B_2 and B_2B_2 three genotypes in both the healthy controls and the CHD patients. The frequencies of B_1B_1, B_1B_2, and B_2B_2 were 45.18%, 39.87%, and 14.95% in the healthy controls and 51.50%, 31.74%, and 16.77% in the CHD patients. The two alleles of B_1 and B_2 appeared 65.12% and 34.88% in the healthy controls and 67.37% and 32.63% in the CHD patients. The I405V locus was detected in II, IV, and VV three genotypes in both the healthy controls and the CHD patients. The frequencies of II, IV, and VV were 15.95%, 48.50%,and 35.55% in the healthy controls and 15.27%, 35.33%, and 49.40% in the CHD patients. The two alleles of I and V appeared 40.20% and 59.80% in the healthy controls and 32.93% and 67.07% in the CHD patients. The D442G locus was detected in DD and DG two genotypes in both the healthy controls and the CHD patients. The frequencies of DD and DG were 95.35% and 4.65% in the healthy controls, and 63.47% and 36.53% in the CHD patients. The two alleles of D and G appeared 97.67% and 2.33% in the healthy controls and 81.74% and 18.26% in the CHD patients. R451Q, A373P or I14A mutations was not detected either in the healthy controls or in the CHD patients. Therefore, the distributions of genotypes and appearing frequencies of alleles at I405V and D442G loci in the CHD patients were significantly different from those in the healthy controls. Conclusion:The polymorphism of I405V and D442G was significantly correlated with CHD in Han ethnic in Hainan province. The V allele of I405V locus was the susceptibility gene, but I allele showed protective effects. The G allele of D442G was the susceptibility gene, and the DG genotype significantly increased the incidence of CHD in Han ethnic in Hainan province.