Methylenetetrahydrofolate reductase gene and coronary artery disease.

Abstract

To the Editor: Brattstrom 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, Brattstrom 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 …