Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US Physicians
Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US Physicians
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DOI：
10.1161/01.cir.94.10.2410
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发表时间：
1996-11-15
期刊：
影响因子：
37.8
通讯作者：
Rozen, R
中科院分区：
文献类型：
--
作者：
Ma, J;Stampfer, MJ;Rozen, R
高同型半胱氨酸血症似乎是冠心病的一个独立危险因素。血浆总同型半胱氨酸（tHCY）水平升高可由同型半胱氨酸代谢的转硫或再甲基化途径中的遗传或营养相关干扰引起。酶5，10-亚甲基四氢叶酸还原酶（MTHFR）催化5，10-亚甲基四氢叶酸还原为5-甲基四氢叶酸，5-甲基四氢叶酸是叶酸的主要循环形式，其作为高半胱氨酸再甲基化为甲硫氨酸的甲基供体。一个常见的突变MTHFR最近已被identified.Methods和结果，我们评估了MTHFR，血浆tHCY，和叶酸的多态性使用基线血液水平之间的293名医生的健康研究参与者谁开发心肌梗死（MI）在长达8年的随访和290名对照组。三种基因型的频率为（-/-）（纯合正常），47%;（+/-）（杂合），41%;和（+/+）（纯合突变），12%，在MI病例患者和对照受试者中具有相似的分布。与（-/-）基因型相比，（-/-）基因型和（+/+）基因型心肌梗死的相对危险度（RR）分别为1.1（95% CI，0.8 ~ 1.5）和0.8（0.5 ~ 1.4），两组RR均无统计学意义。基因型（+/+）组tHCY水平（+/-SEM，12.6 ± 0.5 nmol/mL）高于基因型（-/-）组（10.6 ± 0.3）（P
Background Hyperhomocysteinemia appears to be an independent risk factor for coronary disease. Elevated levels of plasma total homocysteine (tHCY) can result from genetic or nutrient-related disturbances in the transsulfuration or remethylation pathways for homocysteine metabolism. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the predominant circulatory form of folate, which serves as a methyl donor for remethylation of homocysteine to methionine. A common mutation in MTHFR recently has been identified.Methods and Results We assessed the polymorphism in MTHFR, plasma tHCY, and folate using baseline blood levels among 293 Physicians' Health Study participants who developed myocardial infarction (MI) during up to 8 years of follow-up and 290 control subjects. The frequency of the three genotypes was (-/-) (homozygous normal), 47%; (+/-) (heterozygous), 41%; and (+/+) (homozygous mutant), 12%, with a similar distribution among both MI case patients and control subjects. Compared with those with genotype (-/-), the relative risk (RR) of MI among those with (-/-) was 1.1 (95% CI, 0.8 to 1.5), and it was 0.8 (0.5 to 1.4) for the (+/+) genotype; none of these RRs were statistically significant. However, those with genotype (+/+) had an increased mean tHCY level (mean+/-SEM, 12.6+/-0.5 nmol/mL), compared with those with genotype (-/-) (10.6+/-0.3) (P