Folate Gene Polymorphisms MTR A2756G, MTRR A66G, and BHMT G742A and Risk for Coronary Artery Disease: A Meta-Analysis

Context: Folate pathway gene polymorphisms may be a risk factor for coronary artery disease (CAD). However, studies of the association between these polymorphisms and CAD have reported conflicting results. Therefore, we performed a meta-analysis to better assess the association. Objective: To investigate the association between 3 major polymorphisms in genes encoding enzymes involved in remethylation of homocysteine to methionine-methionine synthase (MTR) A2756G, methionine synthase reductase (MTRR) A66G, and betaine homocysteine methyltransferase (BHMT) G742A-and CAD, with assessment of small-study bias and differences between studies. Methods: Case-control studies were identified by searching electronic literature databases for relevant reports published before February 2011. Data on genotype frequency were extracted, and 4 genetic models were applied. Heterogeneity was explored with stratification by ethnicity of the study sample. Results: We found weak evidence of a recessive effect of the G allele in MTR A2756G (odds ratio, 1.61 [95% confidence interval, 0.98-2.66]; p = 0.06). No effect of MTRR A66G and BHMT G742A in dominant, recessive, homozygous, and contrast allele genetic models was observed. Conclusion: Known common single-nucleotide polymorphisms in MTRR and BHMT genes may not be significant risk factors for CAD. The functional impact of these polymorphisms on enzyme activity is still unknown. Before additional epidemiologic studies are done, the functional impact of these polymorphisms, if any, should be established.