Intake of Total and Subgroups of Fat Minimally Affect the Associations between Selected Single Nucleotide Polymorphisms in the PPARγ Pathway and Changes in Anthropometry among European Adults from Cohorts of the DiOGenes Study123

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ABSTRACT

Background: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association.

Objectives: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations.

Methods: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein β (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y.

Results: 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 OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat.

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

KEY WORDS

genetics
fatty acids
gene-diet interaction
obesity
weight change

Abbreviations

BW
body weight
CEBPB
CCAAT/enhancer binding protein β, gene
DiOGenes
European Diet, Obesity and Genes
EPIC
European Prospective Investigation into Cancer and Nutrition
NCBI
National Center for Biotechnology Information
PCK2
phosphoenolpyruvate carboxykinase 2 gene
PPARG
peroxisome proliferator-activated receptor γ gene
PPARγ
peroxisome proliferator-activated receptor γ
SNP
single nucleotide polymorphism
SREBF1
sterol regulatory element-binding transcription factor 1 gene
WC
waist circumference
WCBMI
WC adjusted for BMI
ΔBW
annual change in body weight
ΔWC
annual change in waist circumference
ΔWCBMI
annual change in waist circumference adjusted for BMI

Cited by (0)

1

This work was performed as a part of the research program of Gene-diet interactions in obesity (GENDINOB). GENDINOB is supported by the Danish Council for Strategic Research grant 09-067111.

2

Author disclosures: SC Larsen, L A¨ ngquist, JN Østergaard, TS Ahluwalia, KS Vimaleswaran, N Roswall, LM Mortensen, BM Nielsen, A Tjønneland, NJ Wareham, D Palli, G Masala, WHM Saris, DL van der A, JMA Boer, EJM Feskens, H Boeing, MU Jakobsen, RJF Loos, TIA Sørensen, and K Overvad, no conflicts of interest.

3

Supplemental Figure 1 and Supplemental Tables 1–12 are available from the “Online Supporting Material” link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org.

27

These authors contributed equally to the work.

28

Abbreviations used: BW, body weight; CEBPB, CCAAT/enhancer binding protein β gene; DiOGenes, European Diet, Obesity and Genes; EPIC, European Prospective Investigation into Cancer and Nutrition; NCBI, National Center for Biotechnology Information; PCK2, phosphoenolpyruvate carboxykinase γ gene; PPARGγ, peroxisome proliferator-activated receptor γ gene; PPARγ, peroxisome proliferator-activated receptor γ; SNP, single nucleotide polymorphism; SREBF1, sterol regulatory element-binding transcription factor 1 gene; WC, waist circumference; WCBMI, WC adjusted for ΔMI; ΔBW, annual change in body weight; ΔWC, annual change in waist circumference; ΔWCBMI, annual change in waist circumference adjusted for BMI.