A Common Polymorphism in Methionine Synthase Reductase Increases Risk of Premature Coronary Artery Disease

Citation

Brown, Charlotte A.; McKinney, Kimberly Q.; Kaufman, Jay S.; Gravel, Roy A.; & Rozen, Rima (2000). A Common Polymorphism in Methionine Synthase Reductase Increases Risk of Premature Coronary Artery Disease. Journal of Cardiovascular Risk, 7(3), 197-200.

Abstract

Background: Methionine synthase reductase (MTRR) catalyzes the regeneration of methylcobalamin, a cofactor of methionine synthase, an enzyme essential for maintaining adequate intracellular pools of methionine and tetrahydrofolate, as well as for maintaining homocysteine concentrations at nontoxic levels. We recently identified a common A-->G polymorphism at position 66 of the cDNA sequence of MTRR; this variant was associated with a greater than normal risk for spina bifida in the presence of low levels of cobalamin.
Objective: To investigate whether the polymorphism was associated with alterations in levels of homocysteine, folate, and vitamin B12, and with risk of developing premature coronary artery disease (CAD), in a population of individuals presenting for cardiac catheterization procedures.
Methods: We screened 180 individuals aged < 58 years with angiographically documented coronary-artery occlusions or occlusion-free major arteries for the presence of the 66A-->G MTRR polymorphism using a polymerase-chain-reaction-based assay.
Results: We identified a trend in risk of premature CAD across the genotype groups (P = 0.03) with a sex-adjusted relative risk of premature CAD equal to 1.49 (95% confidence interval 1.10-2.03) for the GG versus AA genotype groups. There was no difference in fasting levels of plasma total homocysteine, serum folate, and vitamin B12 among the three MTRR genotypes.
Conclusions: Our findings suggest that the GG genotype of MTRR is a significant risk factor for the development of premature CAD, by a mechanism independent of the detrimental vascular effects of hyperhomocysteinemia. This association needs to be confirmed in other studies.

URL

http://dx.doi.org/10.1177/204748730000700306

Reference Type

Journal Article

Year Published

2000

Journal Title

Journal of Cardiovascular Risk

Author(s)

Brown, Charlotte A.
McKinney, Kimberly Q.
Kaufman, Jay S.
Gravel, Roy A.
Rozen, Rima