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首页> 外文期刊>Molecular and Cellular Biochemistry >Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease
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Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease

机译：热不稳定性5，10-亚甲基四氢叶酸还原酶基因多态性与高同型半胱氨酸血症与冠心病的关系

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Objective To determine the incidence of methylene tetrahydrofolate reductase (MTHFR) gene 677C→T polymorphism and plasma homocysteine (Hcy) levels in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD) and to investigate the correlation between hyperhomocysteinemia (HHcy) and the presence of 677C→T polymorphism. Background Elevated plasma Hcy level is an independent risk factor for CAD. A common mutation (677C→T) in the gene coding for MTHFR has been reported to reduce the enzymatic activity and is associated with elevated levels of Hcy, especially in subjects with low folate intake. Methods The study group comprised of 84 patients with CAD and 100 age-and-sex matched controls who had no history or clinical evidence of CAD and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with Hinf1, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. Results Allele and genotype frequencies in cases and control subjects were compatible with Hardy–Weinberg equilibrium. The frequencies of TT, CT, and CC genotypes among CAD patients were 4.8, 27.4, and 67.8% and in controls were 1.0, 19.0, and 80%. Hcy levels were higher in patients with triple-vessel disease compared to single and double vessel disease (P = 0.002). Multivariate analyses identified HHcy, diabetes mellitus, and hypertension as the independent predictors of CAD. Conclusions HHcy appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings support that homozygous genotype of MTHFR is a genetic risk factor for CAD. A further study with larger sample size including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.
机译：目的确定一组接受冠状动脉造影的受试者中亚甲基四氢叶酸还原酶（MTHFR）基因677C→T多态性和血浆同型半胱氨酸（Hcy）水平的发生率，以试图建立这些参数与冠状动脉严重程度之间的相关性并研究高同型半胱氨酸血症（HHcy）与677C→T多态性之间的相关性。背景血浆Hcy水平升高是CAD的独立危险因素。据报道，编码MTHFR的基因中常见突变（677C→T）会降低酶的活性，并与Hcy水平升高有关，尤其是在叶酸摄入量较低的受试者中。方法研究组由84例无CAD和/或MI史或临床证据的CAD患者和100名年龄和性别匹配的对照组成。从外周血中提取DNA，并通过聚合酶链反应，Hinf1限制性酶切图和凝胶电泳确定基因型。前瞻性记录了CAD的常规危险因素。结果病例组和对照组的等位基因和基因型频率与Hardy-Weinberg平衡相符。 CAD患者中TT，CT和CC基因型的频率分别为4.8、27.4和67.8％，对照组为1.0、19.0和80％。与单支和双支血管疾病相比，三支血管疾病患者的Hcy水平更高（P = 0.002）。多变量分析确定HHcy，糖尿病和高血压是CAD的独立预测因子。结论HHcy似乎对CAD风险以及冠状动脉粥样硬化的严重程度和程度具有分级影响。我们的发现支持MTHFR的纯合基因型是CAD的遗传危险因素。需要进行更大样本量的进一步研究，包括评估维生素状况，以更好地阐明MTHFR基因型与CAD之间的关系。

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