Background: Genetic variation in SIRT1 has been associated with body mass index (BMI) and risk of obesity. SIRT1 may be influenced by diet.
Objective: We studied the gene-diet interaction on BMI at the SIRT1 locus.
Design: In 4575 elderly men and women in the population-based Rotterdam Study, the effect on BMI of 3 SIRT1 genetic variants (rs7895833, rs1467568, and haplotype 1) was studied in relation to dietary intakes of energy, fat, calcium, milk, antioxidant vitamins, and niacin.
Results: There was no difference in energy or fat intakes by SIRT1 genotype. Significant interactions for BMI were shown between SIRT1 genetic variants and intakes of fat, vitamin E, calcium, and milk. Only the interactions between vitamin E intake and rs1467568 and haplotype 1 remained significant (P < 0.001) after Bonferroni correction for multiple testing. Further analyses across vitamin E-intake tertiles showed highly significant associations of SIRT1 genetic variants with BMI in the lowest tertile [effect sizes (in kg/m(2)): 0.5-0.7 per allele copy; P = 1.9 x 10(-4)-5.7 x 10(-7)] with no associations in the higher tertiles.
Conclusions: Dietary vitamin E intake may modulate the relation of SIRT1 genetic variants with BMI. Associations of SIRT1 variants with BMI in the lowest tertile of vitamin E intake may be explained by low intake of this antioxidant vitamin or by other associated dietary or lifestyle habits. These data provide support that gene-diet interactions influence BMI. Replication of our findings and further in-depth studies of dietary patterns that modify SIRT1 may lead to clinical studies of dietary modification of SIRT1 to influence obesity.