The 2756A>G variant in the gene encoding methionine synthase: its relation with plasma homocysteine levels and risk of coronary heart disease in a Dutch case-control study

M. Klerk, K.J.A. Lievers, L.A.J. Kluijtmans, H.J. Blom, M. Den Heijer, E.G. Schouten, F.J. Kok, P. Verhoef

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65 Citations (Scopus)

Abstract

Introduction: Elevated plasma homocysteine levels have been associated with increased risk of cardiovascular disease. A 2756A>G polymorphism has been found in the gene (MTR) coding for methionine synthase, an enzyme catalyzing remethylation of homocysteine to methionine. Materials and methods: In a Dutch case-control study comprising 123 cases with coronary heart disease (CHD) and 540 controls, we evaluated whether the MTR 2756A>G polymorphism was associated with plasma homocysteine, vitamin B-12, folate concentrations, and CHD risk. Results and conclusions: The polymorphism was not associated with fasting or post-methionine load homocysteine concentrations. Individuals with the GG genotype had 30% lower vitamin B-12 concentrations than individuals with AA or AG genotype (P <0.05). After adjustment for CHD risk factors, the odds ratio (OR) of CHD was 4.0 (95% CI 1.4-11.6) for the GG genotype and 0.7 (95% CI 0.4-1.2) for the AG genotype, when compared to the AA genotype. In conclusion, despite the absence of an association with plasma homocysteine, the GG genotype represented a four-fold increased risk of CUD when compared to the AA genotype. Before putting effort in additional epidemiological studies, it needs to be established first whether this polymorphism has functional consequences for enzyme activity. (C) 2003 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)87-91
JournalThrombosis Research
Volume110
DOIs
Publication statusPublished - 2003

Keywords

  • methylenetetrahydrofolate reductase gene
  • artery-disease
  • myocardial-infarction
  • d919g polymorphism
  • venous thrombosis
  • vascular-disease
  • cdna cloning
  • folate
  • hyperhomocysteinemia
  • association

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