Wilcken D E, Wang X L, Sim A S, McCredie R M
Department of Cardiovascular Medicine, University of New South Wales, Prince Henry/Prince of Wales Hospitals, Sydney, Australia.
Arterioscler Thromb Vasc Biol. 1996 Jul;16(7):878-82. doi: 10.1161/01.atv.16.7.878.
Modest elevations of circulating homocyst(e)ine are common in patients with vascular disease. We explored in normal and coronary artery disease (CAD) populations the distribution of a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene that results in enzyme thermolability and reduced activity and in homocyst(e)ine elevation to assess its relevance to risk. We identified the C to T substitution at the MTHFR locus and compared the distributions of genotypes in 565 patients aged < or = 65 years without and with angiographically documented CAD and in 225 healthy subjects. In the patients, we also assessed interrelations between genotypes and CAD occurrence and severity, as well as standard risk factors. The frequency of homozygotes for the mutation was the same in patients with and without CAD and in healthy subjects (11.6%, 11.0%, and 10.7%, respectively: P > .5 for each). There was also no excess among the 419 patients with severe disease (ie, one or more vessels with > 50% luminal obstruction) compared with those with no or mild CAD (odds ratio: 1.004; 95% confidence interval: 0.59 to 1.70). Homozygosity for the mutation was also not associated with a history of myocardial infarction or the presence or severity of angina. However, body mass index increased linearly with the presence of the mutant allele (P = .005), and the mutation and hypertension were weakly associated (P = .036). We conclude that the MTHFR genotype is not a risk factor for coronary disease in this Australian population but that the strong association found with body mass index should be explored further.
循环中同型半胱氨酸轻度升高在血管疾病患者中很常见。我们在正常人群和冠状动脉疾病（CAD）人群中研究了5,10 - 亚甲基四氢叶酸还原酶（MTHFR）基因中的一种突变的分布情况，该突变导致酶的热不稳定性和活性降低，并引起同型半胱氨酸升高，以评估其与风险的相关性。我们确定了MTHFR位点的C到T替换，并比较了565名年龄≤65岁、经血管造影证实无CAD和有CAD的患者以及225名健康受试者的基因型分布。在患者中，我们还评估了基因型与CAD发生和严重程度之间的相互关系，以及标准风险因素。有CAD和无CAD的患者以及健康受试者中突变纯合子的频率相同（分别为11.6%、11.0%和10.7%：每组P＞0.5）。与无CAD或轻度CAD的患者相比，419名患有严重疾病（即一根或多根血管管腔阻塞＞50%）的患者中也没有过多的突变纯合子（比值比：1.004；95%置信区间：0.59至1.70）。突变纯合子也与心肌梗死病史或心绞痛的存在及严重程度无关。然而，体重指数随突变等位基因的存在呈线性增加（P = 0.005），并且突变与高血压存在弱相关性（P = 0.036）。我们得出结论，在这个澳大利亚人群中，MTHFR基因型不是冠心病的风险因素，但与体重指数的强相关性值得进一步研究。
