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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 Study.

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Larsen, Sofus C 
Ängquist, Lars 
Østergaard, Jane N 
Ahluwalia, Tarunveer S 
Vimaleswaran, Karani S 


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.



fatty acids, gene-diet interaction, genetics, obesity, weight change, Adult, Alleles, Body Mass Index, CCAAT-Enhancer-Binding Protein-beta, Case-Control Studies, Cohort Studies, Diet, Dietary Fats, Fatty Acids, Fatty Acids, Monounsaturated, Fatty Acids, Unsaturated, Female, Follow-Up Studies, Genotyping Techniques, Humans, Linkage Disequilibrium, Male, Middle Aged, Nutrition Assessment, PPAR gamma, Phosphoenolpyruvate Carboxykinase (ATP), Polymorphism, Single Nucleotide, Sterol Regulatory Element Binding Protein 1, Waist Circumference, Weight Gain, White People

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J Nutr

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Elsevier BV
MRC (MC_PC_13048)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MC_U106179471)