冠心病患者同型半胱氨酸代谢相关酶基因多态性的研究  

Genetic polymorphisms of homocysteine metabolism related enzymes in patients with coronary heart disease

作　　者：许海燕[1,2,3] 陈在嘉[1,2,3] 汤健[1,2,3] 姜玉新[1,2,3] 张晨晖[1,2,3] 朱大明[1,2,3] 张春玲[1,2,3] 叶珏[1,2,3] 赵如冰 杨跃进[1,2,3] 陈纪林[1,2,3] 惠汝太[1,2,3] 

机构地区：[1]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院冠心病研究室 [2]北京医科大学心血管研究所 [3]中国妇婴保健中心

出　　处：《中华医学杂志》1999年第6期414-416,共3页National Medical Journal of China

摘　　要：目的研究冠心病患者同型半胱氨酸代谢相关酶甲烯四氢叶酸还原酶（ＭＴＨＦＲ）基因Ｃ６７７Ｔ和胱硫醚缩合酶（ＣＢＳ）基因Ｔ８３３Ｃ位碱基突变。方法对２０９例冠心病患者和１０１例健康对照者，采用多聚酶链反应限制性内切酶片段长度多态性技术检测ＭＴＨＦＲＣ６７７Ｔ基因型，用扩增阻滞突变体系法检测ＣＢＳ基因Ｔ８３３Ｃ多态性，采用高压液相色谱法测定同型半胱氨酸血浆水平。结果患者组ＭＴＨＦＲ基因Ｔ纯合基因型和杂合基因型频率（分别为２７．８％和４５．４％）显著高于正常对照组（分别为２２．８％和３４．６％），两组基因型和等位基因频率分布差异有显著意义（Ｐ＜０．０５）。ＣＢＳ基因在患者组发现２１例突变纯合子，正常组中发现２例突变纯合子，两组基因型和等位基因频率分布差异有非常显著意义（Ｐ＜０．００１），同时，患者组和正常对照组ＭＴＨＦＲ和ＣＢＳ基因突变者血浆同型半胱氨酸水平均高于无基因突变者。结论显示高同型半胱氨酸血症可能是中国人较早发冠心病的一个独立危险因素，而ＭＴＨＦＲ基因Ｃ６７７Ｔ点突变和ＣＢＳ基因Ｔ８３３Ｃ点突变可能是其发病的重要遗传因素。Objective To study genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and cystathionine β synthase(CBS) T833C related to homocysteine metabolism in patients with coronary heart disease (CHD). Methods 209 patients with CHD and 101 controls were selected. MTHFR genetic C677T polymorphism was determined by PCR RFLP, and CBS T833C polymorphism by ARMS method. Plasma homocysteine levels were detected with HPLC. Results The frequencies of MTHFR T homogenetic type and heterogenetic type (27.8% and 45.4%) in case group were higher than those in normal group(22.8% and 34.6%). There were significant differences in the frequencies of genotypes and alleles between two groups ( P <0 05). C homogenotype of CBS gene was found in 21 patients, and 2 in the normal group. There were evident differences in the frequencies of genotypes and alleles of the two groups ( P <0.001). Morover, plama homocysteine levels were markedly higher in patients with MTHFR or CBS genetic mutation than those in patients without mutation( P <0.05). Conclusions Hyperhomocysteinemia is an independent risk factor of CHD. MTHFR and CBS are the main enzymes related to homocysteine metabolism. Their genetic mutations are possibly important mechanism of hyperhomocysteinemia and coronary heart disease.

关 键 词：冠心病 同型 半胱氨酸 MTHFR CBS 基因多态性 

分 类 号：R541.4[医药卫生—心血管疾病]