Interaction between Mediterranean diet and methylenetetrahydrofolate reductase C677T mutation on oxidized low density lipoprotein concentrations: The ATTICA study

Abstract

Background The oxidative modification of low-density lipoprotein (LDL) has been suggested to be a key element in atherogenesis, while methylenetetrahydrofolate reductase (MTHFR) C677T mutation has been associated with the development of coronary heart disease. We evaluated whether adoption of a Mediterranean type of diet is associated with oxidized LDL levels, as well as the role of MTHFR C677T mutation in this relationship. Methods We studied demographics, lifestyle, clinical, biochemical and genetic data from 322 men (46±13 years) and 252 women (45±14 years), without any clinical evidence of cardiovascular disease, from the Attica region, Greece (i.e. the ATTICA study). Among the other parameters we also measured oxidized (ox)-LDL levels, and the distribution of MTHFR. Adherence to the Mediterranean diet was evaluated by a special diet score. Results The distribution of MTHFR genotypes was: 41% for homozygous normal (CC) genotype, 48% for heterozygous (CT) and 11% for homozygous mutant (TT) genotype. Ox-LDL levels were higher in TT as compared to CC and CT (70.8±26 vs. 51.0±26 vs. 63.7±24 mg/dl, p<0.001). Greater adherence to the Mediterranean diet was inversely associated with ox-LDL levels (standardized beta=−0.34, p<0.001), after controlling for several confounding variables; however, stratified analysis revealed that adherence to the Mediterranean diet was associated with lower ox-LDL levels in TT and CT individuals (standardized beta=−0.67, p=0.001 and standardized beta=−0.66, p=0.025, respectively), but not in CC (standardized beta=−0.18, p=0.10), after controlling for several potential confounders. Conclusion The observed gene-to-diet interaction on ox-LDL concentrations may provide a pathophysiological explanation by which a Mediterranean type of diet could influence coronary risk in people with increased oxidative stress.