Influence of a methionine synthase (D919G) polymorphism on plasma homocysteine and folate levels and relation to risk of myocardial infarction
Influence of a methionine synthase (D919G) polymorphism on plasma homocysteine and folate levels and relation to risk of myocardial infarction
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DOI：
10.1016/s0021-9150(00)00469-x
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发表时间：
2001-02-15
期刊：
影响因子：
5.3
通讯作者：
Hunter, DJ
中科院分区：
文献类型：
--
作者：
Chen, J;Stampfer, MJ;Hunter, DJ
甲硫氨酸合成酶（MS）编码一种酶，该酶使用5-甲基四氢叶酸（体内主要循环形式的叶酸）提供的甲基催化高半胱氨酸重新甲基化为甲硫氨酸。MS的功能性遗传变异可能会改变总同型半胱氨酸（tHcy）以及叶酸水平，这是血管疾病的独立危险因素。在一项针对美国男性医生的前瞻性研究中，研究了MS基因的常见遗传多态性（2756 A--> G，D19 G）对血浆tHcy和叶酸水平的影响及其与心肌梗死（MI）风险的关系。在医生健康研究中进行了一项嵌套病例对照研究，该研究最初设计为1982年在22 071名40-84岁的美国男性医生中进行阿司匹林和β-胡萝卜素的双盲试验。68%的参与者还捐献了血液样本。该研究包括387例心肌梗死病例和767例年龄匹配的对照。吸烟状态和从随机化开始的时间，间隔为6个月。在调整MI危险因素后，GG基因型个体与DD基因型个体相比MI风险无显著降低（RR 0.51，95%CI 0.17-1.16）。DD、DG和GG基因型的tHcy分别为10.55、9.87和9.57 nmol/ml。分别）和增加叶酸水平（3.95，3.78，7.31 ng/ml。DG和GG基因型）仅在对照组中而非病例中。结论是MS（D919 G）多态性对血浆tHcy和叶酸水平的影响最多为中度，但应在其他大型前瞻性研究中进一步研究。(C)2001爱思唯尔科学爱尔兰有限公司保留所有权利。
Methionine synthase (MS) encodes an enzyme that catalyzes the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetrahydrofolate, which is the major circulating form of folate in the body. Functional genetic variants of the MS may alter total homocysteine (tHcy) as well as folate levels which are independent risk factors for vascular disease. The influence of a common genetic polymorphism (2756A --> G, D19G) of the MS gene on plasma tHcy and folate levels and its relation to the risk of myocardial infarction (MI) in a prospective study of male physicians in the US was investigated. A nested case-control study was conducted within the Physicians Health Study which was originally designed as a double-blind trial of aspirin and beta-carotene among 22 071 US male physicians, aged 40-84 years in 1982. Sixty-eight percent of participants also donated a blood sample. The study included 387 incident MI case and 767 controls matched on age. smoking status. and time From randomization in 6-month intervals. Individuals with GG genotype had a non-significant reduction of MI risk (RR 0.51, 95% CI 0.17-1.16) compared to individuals with DD genotype after adjusting for MI risk factors. The MS polymorphism was associated with decreased tHcy (10.55, 9.87 and 9.57 nmol/ml for DD, DG and GG genotypes. respectively) and increased folate levels (3.95, 3.78. 7.31 ng/ml for DD. DG and GG genotypes, respectively) only among controls but not cases. It was concluded that influence of the MS (D919G) polymorphism on the plasma tHcy and folate levels is at most moderate, but should be further investigated in other large prospective studies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.