Influence of a methionine synthase (D919G) polymorphism on plasma homocysteine and folate levels and relation to risk of myocardial infarction

Methionine synthase (MS) encodes an enzyme that catalyzes the remethylation of homocysteine to methionine using a methyl group donated by 5-methyltetr ahydrofolate, which is the major circulating form of folate in the body. Fu nctional genetic variants of the MS may alter total homocysteine (tHcy) as well as folate levels which are independent risk factors for vascular disea se. The influence of a common genetic polymorphism (2756A --> G, D19G) of t he 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 th e US was investigated. A nested case-control study was conducted within the Physicians Health Study which was originally designed as a double-blind tr ial of aspirin and beta-carotene among 22 071 US male physicians, aged 40-8 4 years in 1982. Sixty-eight percent of participants also donated a blood s ample. The study included 387 incident MI case and 767 controls matched on age. smoking status. and time From randomization in 6-month intervals. Indi viduals with GG genotype had a non-significant reduction of MI risk (RR 0.5 1, 95% CI 0.17-1.16) compared to individuals with DD genotype after adjusti ng for MI risk factors. The MS polymorphism was associated with decreased t Hcy (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 gen otypes, respectively) only among controls but not cases. It was concluded t hat influence of the MS (D919G) polymorphism on the plasma tHcy and folate levels is at most moderate, but should be further investigated in other lar ge prospective studies. (C) 2001 Elsevier Science Ireland Ltd. All rights r eserved.