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Effect of interaction between adherence to a Mediterranean diet and the methylenetetrahydrofolate reductase 677CT mutation on homocysteine concentrations in healthy adults: the ATTICA Study^1,2,3

¹ From the Department of Science in Dietetics and Nutrition, Harokopio University, Athens, Greece (GVD, DBP, AZ, and DC), and the First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece (CC, CP, and CS)

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) 677CT 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 ( ± 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 ( ± SD: 15.8 ± 9 compared with 11.3 ± 8 and 10.8 ± 9 µmol/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 (ß = –0.21, P = 0.002, and ß = –0.14, P = 0.025, respectively) but not in those with the CC genotype (ß = –0.03, P = 0.38).

Conclusion: The observed association of an MTHFR 677CT 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.

Key Words: Homocysteine • methylenetetrahydrofolate reductase • MTHFR genotype • cardiovascular disease • Mediterranean diet

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