Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease
Genetic polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease
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DOI：
10.1161/01.cir.95.8.2032
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发表时间：
1997-04-15
期刊：
影响因子：
37.8
通讯作者：
Yazaki, Y
中科院分区：
文献类型：
--
作者：
Morita, H;Taguchi, J;Yazaki, Y
流行病学研究已经确定高同型囊(e)血症是冠状动脉疾病（CAD）的独立危险因素。近年来，催化同型半胱氨酸再甲基化的关键酶之一- 5,10-亚甲基四氢叶酸还原酶（MTHFR）基因的丙氨酸/缬氨酸（AN）多态性被报道。VV基因型与血浆同囊氨酸水平升高相关，这是由于该酶活性降低和耐热性增加的结果。在这项研究中，我们检测了日本男性中MTHFR基因型的分布以及VV基因型与CAD之间的关系。方法与结果所有患者均经冠状动脉造影诊断为冠心病。采用PCR分析MTHFR基因型，并进行HinfI消化。在778名健康男性受试者中，V等位基因的频率为0.33，与法裔加拿大人的频率相当。在362例CAD患者中，VV基因型明显高于对照组（16%对10%，P= 0.0067）。在狭窄病变大于或等于99%的患者中，VV基因型与CAD的相关性进一步增加（18%，P= 0.0010），而在狭窄不大于或等于99%的患者中，VV基因型与CAD的相关性不显著。当比较不同冠状动脉数目狭窄患者的基因型频率时，三支血管病变患者的VV基因型频率（26%）明显高于单支或双支血管病变患者（分别为15%和14%）。结论MTHFR的VV基因型在日本人群中也很常见，且与CAD有显著相关性。这种基因型的频率尤其与疾病的严重程度相关。与血浆同型囊(e)线水平升高倾向相关的VV基因型可能是CAD的遗传危险因素。
Background Epidemiological studies have identified hyperhomocyst(e)inemia as an independent risk factor for coronary artery disease (CAD). Recently, the alanine/valine (AN) polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, one of the key enzymes catalyzing remethylation of homocysteine, has been reported. The VV genotype correlates with increased plasma homocyst(e)ine levels as a result of the reduced activity and increased thermolability of this enzyme. In this study, we examined the distribution of the MTHFR genotypes in Japanese men and the association between the VV genotype and CAD.Methods and Results The diagnoses of CAD of all the studied patients were confirmed by coronary angiography. The MTHFR genotype was analyzed by PCR followed by HinfI digestion. In 778 healthy male subjects, the frequency of the V allele was 0.33, comparable to that in a French Canadian population. In 362 patients with CAD, the VV genotype was significantly more frequent than in control subjects (16% versus 10%, P=.0067). The association of the VV genotype with CAD was further increased in patients with greater than or equal to 99% stenotic lesions (18%, P=.0010), whereas no significant association with the VV genotype was observed in patients without a greater than or equal to 99% stenosis. When the genotype frequency was compared among patients with different numbers of stenotic coronary arteries, the frequency of the VV genotype was significantly higher in patients with triple-vessel disease (26%) than in patients with single- or double-vessel disease (15% and 14%, respectively).Conclusions The VV genotype of MTHFR was also common in the Japanese population and was significantly associated with CAD. The frequency of this genotype in particular was correlated with the severity of disease. The VV genotype associated with a predisposition to increased plasma homocyst(e)ine levels may represent a genetic risk factor for CAD.