Intake of total and subgroups of fat minimally affect the associations between selected SNPs in the PPARγ pathway and changes in anthropometry among European adults from cohorts of the DiOGenes Study

Although the PPARγ pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether intake of dietary fat has a modifying effect on the association. We examined whether 27 SNPs within four genes in the PPARγ pathway are associated with the odds ratio (OR) of being a BW gainer or with annual changes in anthropometry, and whether dietary intake of total fat, monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), or saturated fat acids (SFAs) have a modifying effect on these associations.

A case/non-case study including 11,048 men and women from cohorts in the European DiOGenes study; 5,552 of these participants were cases, defined as individuals with the greatest BW gain during follow-up, and 6,548 were randomly selected, of which 5,496 were non-cases. We selected four genes based on evidence regarding biologic plausibility for interactions with dietary fat in body fat regulation (CEBPB, PCK2, PPARG, and SREBF1).

Diet was assessed at baseline, and anthropometric changes were followed for seven years. The OR of being a BW gainer was assessed using logistic regression and annual changes in anthropometry were analyzed using linear regression. The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele.

Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The ORs for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher fat intake where 1.07 (95% CI: 1.02, 1.12; P=0.008) for total fat, 1.20 (95% CI: 1.05, 1.36; P=0.006) for MUFAs, 1.34 (95% CI: 1.04, 1.73; P=0.02) for PUFAs, and 1.14 (95% CI: 1.02, 1.28; P=0.02) for SFAs.

Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and the OR of BW gain or changes in anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.