Effect of interaction between adherence to a Mediterranean diet and the methylenetetrahydrofolate reductase 677C→T mutation on homocysteine concentrations in healthy adults:: the ATTICA Study

Background: Dietary and genetic factors may influence the effect of raised homocysteine concentrations on coronary artery disease risk. Objective: We evaluated the effect of the interaction between adoption of a Mediterranean diet and the methylenetetrahydrofolate reductase gene (MTHFR) 677C-->T mutation on homocysteine concentrations in healthy adults participating in the ATTICA study. Design: We studied demographic, lifestyle, clinical, biochemical, and genetic information from 322 men ((x) over bar +/- SD age: 46 +/- 13 y) and 252 women (45 +/- 14 y) who had no clinical evidence of cardiovascular or any other chronic disease. We also measured total plasma homocysteine concentrations, the distribution of the MTHFR genotype, and adherence to a Mediterranean diet. Results: The distribution of MTHFR genotypes was as follows: homozygous normal (CC), 41%; heterozygous (CT), 48%; and homozygous mutant (TT), 11%. Homocysteine concentrations were higher in persons with the TT genotype than in those with the CC and CT genotypes ((x) over bar +/- SD: 15.8 +/- 9 compared with 11.3 +/- 8 and 10.8 +/- 9 mumol/L, respectively; P < 0.001). The Mediterranean diet score was not significantly associated with homocysteine concentrations (P = 0.89). However, after control for potential confounders, the stratified analysis showed that adherence to a Mediterranean diet was associated with reduced homocysteine concentrations in persons with the TT and CT genotypes (beta = -0.21, P = 0.002, and beta = -0.14, P = 0.025, respectively) but not in those with the CC genotype (beta = -0.03, P = 0.38). Conclusion: The observed association of an MTHFR 677C-->T gene-diet interaction on homocysteine concentrations may provide a pathophysiologic explanation for how a Mediterranean diet may influence coronary risk in persons with raised homocysteine concentrations.