Larsen Sofus C, Ängquist Lars, Østergaard Jane N, Ahluwalia Tarunveer S, Vimaleswaran Karani S, Roswall Nina, Mortensen Lotte M, Nielsen Birgit M, Tjønneland Anne, Wareham Nicholas J, Palli Domenico, Masala Giovanna, Saris Wim H M, van der A Daphne L, Boer Jolanda M A, Feskens Edith J M, Boeing Heiner, Jakobsen Marianne U, Loos Ruth J F, Sørensen Thorkild I A, Overvad Kim
Research Unit for Dietary Studies at the Parker Institute, Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark; Department of Cardiology, Cardiovascular Research Center, Aalborg University Hospital, Aalborg, Denmark;
Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark;
J Nutr. 2016 Mar;146(3):603-11. doi: 10.3945/jn.115.219675. Epub 2016 Feb 10.
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.
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.
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.
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.
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.
尽管过氧化物酶体增殖物激活受体γ（PPARγ）途径在脂肪生成中起核心作用，但该途径是否影响体重（BW）变化以及膳食脂肪是否对这种关联具有调节作用仍不清楚。
我们研究了PPARγ途径中4个基因内的27个单核苷酸多态性（SNP）是否与体重增加者的比值比（OR）相关，或与人体测量学的年度变化相关，以及总脂肪、单不饱和脂肪、多不饱和脂肪或饱和脂肪的摄入量是否对这些关联具有调节作用。
一项病例-非病例研究纳入了欧洲饮食、肥胖与基因研究队列中的11,048名男性和女性；5552例为病例，定义为随访期间体重增加最多的个体，6548例为随机选择，包括5496例非病例。根据与膳食脂肪在体重调节中相互作用的生物学合理性证据，我们选择了4个基因[CCAAT/增强子结合蛋白β（CEBPB）、磷酸烯醇式丙酮酸羧激酶2、PPARγ基因（PPARG）和固醇调节元件结合转录因子1]。在基线时评估饮食，并对人体测量学进行7年随访。
每增加一个次要等位基因，27个基因变异成为体重增加者的OR范围为0.87（95%CI：0.79，1.03）至1.12（95%CI：0.96，1.22）。未经校正时，CEBPB rs4253449与总脂肪摄入量及脂肪亚组存在显著相互作用。每100千卡总脂肪摄入量增加，rs4253449每增加一个次要等位基因成为体重增加者的OR为1.07（95%CI：1.02，1.12；P = 0.008），脂肪亚组也发现了类似关联。
在欧洲男性和女性中，膳食脂肪对PPARγ途径中SNP与人体测量学之间关联的影响可能不存在或很微小。rs4253449与膳食脂肪之间观察到的相互作用需要进一步证实。
