亚甲基四氢叶酸还原酶基因多态性及血中同型半胱氨酸和叶酸水平与冠心病的关系  

Methylenetetrahydrofolate reductase gene polymorphism, homocysteine,folate and coronary artery disease

作　　者：方理刚[1] 朱文玲[1] 朱广瑾[2] 鄢盛凯[3] 

机构地区：[1]中国医学科学院中国协和医科大学北京协和医院心内科,100730 [2]中国医学科学院中国协和医科大学基础医学研究所 [3]中国医学科学院中国协和医科大学北京协和医院检验科,100730

出　　处：《中华心血管病杂志》2002年第9期515-519,共5页Chinese Journal of Cardiology

摘　　要：目的　观察高同型半胱氨酸 (HCY)血症是否为中国人冠心病 (CHD)的一个独立危险因素 ,以及探讨亚甲基四氢叶酸还原酶 (MTHFR)基因多态性与冠心病的联系 ,并分析HCY、叶酸与MTHFR基因多态性间的相互关系。方法　选择CHD患者 16 1例 ,其中 15 4例行冠状动脉造影证实。正常对照 12 5例。应用荧光免疫偏振法测定血浆HCY ,放免法测定血清叶酸 ,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 (15 2 4± 9 5 9)与 (11 4 3± 6 4 4 ) μmol L ,P <0 0 1]。logistic回归分析显示性别、年龄、脂蛋白B和高HCY血症是CHD发病的独立危险因素 ,高HCY血症的优势比 (OR)为 2 5 70 7,其 95 %的可信区间 1 30 0 3～ 5 0 82 5。CHD组MTHFR基因C6 77T突变TT型的频率为 2 9 2 % ,明显高于对照组 16 8% (P =0 0 15 )。CHD组T等位基因频率显著高于对照组 (P =0 0 0 4 )。CHD组和对照组TT型的血浆HCY水平明显高于CT和CC型 (P <0 0 0 1)。CHD组各基因型的HCY水平均高于对照组 (P <0 0 0 1～ 0 0 1)。多元逐步回归显示 :血清叶酸浓度、TT型与血浆HCY浓度独立相关。CHD组和对照组的TT型中 ,血清叶酸水平 <对照组中位数时的HCY水平显著高于叶酸≥中位数时的HCY值。叶酸 <中位数时 。Objective To investigate if hyperhomocysteinemia is an independent risk factor associated with coronary heart disease(CHD) and to detect the association of MTHFR polymorphism with CHD, furthermore, to analyze the relationships among HCY, folate and MTHFR gene.Methods In 161 patients with CHD who was verified by coronary angiograms (CHD group)and 125 control subjects without CHD, the serum folate and vitamin B 12 were measured by radioimmunoassay and the plasma HCY by fluorescence polarization immunoassay. The MTHFR polymorphism was determined by polymerase chain reaction. Results The plasma HCY level was significantly higher in CHD cases than in control [(15 24±9 59) μmol/L vs. (11 43±6 44)μmol/L, P <0 01]. Logistic regression analysis indicated that sex, age, ApoB and HCY were independent risk factors for CHD. The odds ratios (OR) of hyperhomocysteinemia for CHD was 2 5707(95% confidence interval, 1 300 3 to 5 082 5). The frequency of the MTHFR TT genotype in CHD cases was 29 2%, which was significantly higher than that in control subjects (16 8%) , P =0 015.The frequency of T allele in CHD cases increased significantly compared with that in control subjects ( P =0 004).The plasma HCY level in CHD cases and control subjects with TT genotype was significantly higher than that with CT or CC genotype. The plasma HCY levels for different genotypes were significantly higher in CHD cases than those in control subjects. The plasma HCY level was negatively correlated with the serum folate level in both CHD and control group. Multivariate stepwise regression indicated that folate level and MTHFR TT genotype were independently related to the plasma HCY level. The highest plasma HCY level occurred in CHD subgroup with TT type and folate below the median. In CHD cases with serum folate levels at or above the sample median, there were no differences in HCY levels among the MTHFR genotypes. In CHD or control cases with serum folate below the median, plasma HCY was significantly hig

关 键 词：亚甲基四氢叶酸还原酶 基因多态性 同型半胱氨酸 叶酸 冠心病 

分 类 号：R541.4[医药卫生—心血管疾病]