This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mager, A. Articles by Öhrvik, J. Search for Related Content PubMed PubMed Citation Articles by Mager, A. Articles by Öhrvik, J.

(Circulation. 2000;101:e172.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Methylenetetrahydrofolate Reductase Gene and Coronary Artery Disease

A. Mager, MD

Department of Cardiology Rabin Medical Center

Petah Tiqva

Tel Aviv University, Tel Aviv, Israel

	Introduction

 
To the Editor:

Brattström et al¹ performed a meta-analysis of the results of 13 studies on plasma homocysteine concentrations in the 3 genotypes of the C677T mutation of the enzyme methylenetetrahydrofolate reductase (MTHFR) and of 23 case-control studies on this mutation in cardiovascular disease. They found that the TT (homozygous mutant) genotype was associated with mildly elevated plasma homocysteine concentrations but with a relative risk of vascular disease of only 1.12. They concluded that although the C677T mutation of MTHFR is a major cause of mild hyperhomocysteinemia, it is not a risk factor for cardiovascular disease.

We are greatly concerned by this meta-analysis, particularly by the inclusion of different populations. The impact of the C677T mutation on plasma homocysteine and its association with coronary artery disease (CAD) reflect a gene-environment interaction. However, Brattström et al pooled data from populations that differed in their ethnic origin, geographic location, and probably nutritional status. A review of the pooled studies on MTHFR polymorphism in CAD and of more recent works, including a preliminary report from our institution,² shows that almost all the negative studies included populations of Anglo-Saxon origin, whereas all the positive studies included populations of other ethnic origins: Dutch,³ Irish,⁴ Japanese,⁵ and Israeli Jews.² This suggests that the association between MTHFR polymorphism and CAD is population specific and cannot be subjected to meta-analysis.

Although it is not yet clear why the role of MTHFR C677T as a risk factor for CAD varies among populations, differences in plasma homocysteine levels in homozygotes . . . [Full Text of this Article]

Dr Lars Brattström

Department of Medicine

Lars Brudin

Department of Clinical Physiology County Hospital, Kalmar, Sweden

Prof David E.L. Wilcken

Cardiovascular Genetics Laboratory University of New South Wales, Prince of Wales Hospital, Sydney, Australia

John Öhrvik

Department of Statistics University of Agricultural Sciences, Uppsala, Sweden