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(Circulation. 1998;98:2932-2935.)
© 1998 American Heart Association, Inc.

Correspondence

Methylenetetrahydrofolate Reductase Mutation and Coronary Artery Disease

N. J. Samani, MD, FRCP

Department of Cardiology University of Leicester, Leicester, UK

To the Editor:

The article by Kluijtmans and colleagues¹ (Circulation, October 21, 1997) adds to the growing literature on the relationship between the common thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) and risk of vascular disease. In an angiographically assessed cohort of subjects with coronary artery disease (CAD) participating in a statin regression trial (REGRESS), significantly increased homocysteine concentrations were found in subjects homozygous (+/+) or heterozygous (+/-) for the thermolabile variant compared with those carrying only the normal variant (-/-). Median levels were 2.8 and 0.8 µmol/L higher in the +/+ and +/- subjects, respectively. Compared with population-based controls, there was trend toward higher risk of CAD in subjects carrying the thermolabile variant, but this did not reach significance (OR for +/+ versus -/-: 1.21 [0.87 to 1.68]; +/- versus -/-: 1.14 [0.94 to 1.38]). However, when the results were combined with those of 6 other studies, including our own,² in a meta-analysis, there was a significant increase in relative risk in subjects with the +/+ genotype (OR, 1.22; 95% CI, 1.10 to 1.47).

The data of Kluijtmans et al in a large cohort of well-characterized CAD patients are welcome. However, I am concerned by their meta-analysis. They have pooled together data from studies that have examined different phenotypes. For example, in our study,² we recruited subjects with myocardial infarction. Although there is, of course, a relationship between angiographic CAD and myocardial infarction, the 2 are not synonymous, and each has distinct determinants. This is likely to extend . . . [Full Text of this Article]

L. A. J. Kluijtmans, MSc; H. J. Blom, PhD

Department of Pediatrics

G. H. J. Boers, MD, PhD

Department of Internal Medicine

F. Willems, MD

Department of Cardiology University Hospital Nijmegen, Nijmegen, Netherlands

D. E. L. Wilcken

The University of New South Wales Department of Cardiovascular Medicine, The Prince of Wales Hospital, Sydney, New South Wales, Australia