亚甲基四氢叶酸还原酶基因多态性及同型半胱氨酸水平与冠心病的关系

Methylenetetrahydrofolate reductase gene polymorphism,homocysteine and coronary heart disease

目的观察高同型半胱氨酸(HCY)是否是冠心病的一个独立危险因素,并探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与冠心病(CHD)的联系。方法选择CHD患者80例,对照组70例。应用荧光偏振免疫分析法测定血浆HCY,以聚合酶链反应-限制性内切酶片段长度多态性(PCR-RELP)分析MTHFR基因多态性。结果CHD患者血浆HCY浓度显著高于对照组[分别为(17±11)μmol/L与(12±7)μmol/L,P<0.01]。MTHFR有3种基因型,即纯合子突变(TT)、杂合子突变(TC)及野生纯合型(CC)。CHD组TT型、TC型、CC型基因频率分布及T、C等位基因频率与对照组比较差异无统计学意义(χ2=3.213,P>0.05;χ2=1.836,P>0.05)。CHD组和对照组的TT型的血浆HCY水平明显高于TC型和CC型(P<0.01)。Logistic回归分析显示高HCY血症是CHD发病的独立危险因素,其OR值为3.108,95%可信区间1.426～6.775。结论高HCY血症是CHD发病的独立危险因素。MTHFR基因的C677T突变是高同型半胱氨酸血症的原因,但MTHFRC677T基因多态性与冠心病的发生无显著相关。

Objective To investigate whether hyperhomocysteinemia is an independent risk factor associated with coronary heart disease （CHD）and to detect the association of MTHFR polymorphism with CHD.Methods In 80 patients with CHD and 70 control subjects without CHD, the plasma HCY concentration was measured by fluorescence polarization immunoaszay.The MTHFR polymorphism was determined by PCR-RELP.Results The plasma HCY level was significantly higher in CHD group than in control [（17±11μmol/L）vs （12±7μmol/L）,P〈0.01].There were three kinds of genotype：homozygous mutation （TT）,heterozygous mutation （TC）,wild-type （CC）.There was no significant difference in the frequencies of genotype and alleles between two groups （X^2=3.213,P〉0.05.X^2=1.836,P〉0.05）.The plasma HCY level in CHD and control subjects with TT genotype was significantly higher than that with CT or CC genotype.Logistic-regression analysis indicated that HCY was an independent risk factors for CHD.The odds ratios （OR）of hyperhomocysteinemia for CHD was 3.140 （95% confidence interval,1.431 to 6.889）.Conclusions Hyperhomocysteinemia may be an independent risk factor for CHD.MTHFR C677T genotype may be an important mechanism of hyperhomocysteinemia,but MTHFR mutation is not related with CHD.