Abstract
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, D919G) 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.
Keywords
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Article info
Publication history
Accepted:
March 2,
2000
Received in revised form:
February 7,
2000
Received:
November 5,
1999
Identification
Copyright
© 2001 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
