A common polymorphism in methionine synthase reductase increases risk of premature coronary artery disease

J Cardiovasc Risk. 2000 Jun;7(3):197-200. doi: 10.1177/204748730000700306.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Base Sequence
  • Coronary Disease / blood
  • Coronary Disease / genetics*
  • Data Interpretation, Statistical
  • Female
  • Ferredoxin-NADP Reductase / genetics*
  • Flavoproteins / genetics*
  • Folic Acid / blood
  • Genotype
  • Homocysteine / blood
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Regression Analysis
  • Risk
  • Sex Factors
  • Vitamin B 12 / blood

Substances

  • Flavoproteins
  • Homocysteine
  • Folic Acid
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • Vitamin B 12