Ruchat Stephanie-May, Elks Cathy E, Loos Ruth J F, Vohl Marie-Claude, Weisnagel S John, Rankinen Tuomo, Bouchard Claude, Pérusse Louis
Department of Preventive Medicine, Laval University, Québec, Canada.
J Nutrigenet Nutrigenomics. 2009;2(4-5):225-34. doi: 10.1159/000259341. Epub 2010 Mar 9.
BACKGROUND/AIMS: Genome-wide association studies have led to the identification of several susceptibility genes for type 2 diabetes mellitus (T2DM). The objective of this study was to test the hypothesis that the associations between single nucleotide polymorphisms (SNPs) in these genes and adiposity and glucose homeostasis-related phenotypes are influenced by dietary fat intake.
Thirty-three SNPs in 9 T2DM genes (CDKAL1, CDKN2A/B, HHEX, HNF1B, IGF2BP2, KCNJ11, SLC30A8, TCF7L2 and WFS1) were tested in a maximum of 669 subjects from the Quebec Family Study. Subjects were measured for several adiposity indices and underwent a 75-gram oral glucose tolerance test. Total fat intake was estimated from a 3-day dietary record.
We observed 13 significant (p < or = 0.01) SNP-dietary fat interactions. Among them, IGF2BP2 rs4402960, alone or in interaction with dietary fat intake, influenced abdominal total fat (ATF: SNP effect, p = 0.006, interaction effect, p = 0.009) and abdominal visceral fat (AVF: SNP effect, p = 0.007, interaction effect, p = 0.01). Similarly, TCF7L2 rs12573128 alone or in interaction with dietary fat intake, influenced insulin sensitivity (SNP effect and interaction effect, p < or = 0.008) and glucose tolerance (SNP effect p < or= 0.009 and interaction effect, p < or = 0.01).
These results suggest that gene-dietary fat interactions may influence glucose homeostasis-related phenotypes and play an important role in determining the increased risk of diabetes associated with the T2DM susceptibility genes.
背景/目的：全基因组关联研究已鉴定出2型糖尿病（T2DM）的多个易感基因。本研究的目的是检验以下假设：这些基因中的单核苷酸多态性（SNP）与肥胖及葡萄糖稳态相关表型之间的关联受膳食脂肪摄入量的影响。
在魁北克家族研究中，对9个T2DM基因（CDKAL1、CDKN2A/B、HHEX、HNF1B、IGF2BP2、KCNJ11、SLC30A8、TCF7L2和WFS1）中的33个SNP进行检测，样本最多669例。测量受试者的多个肥胖指数，并进行75克口服葡萄糖耐量试验。通过3天饮食记录估算总脂肪摄入量。
我们观察到13个显著（p≤0.01）的SNP-膳食脂肪相互作用。其中，IGF2BP2 rs4402960单独或与膳食脂肪摄入相互作用时，会影响腹部总脂肪（ATF：SNP效应，p = 0.006，相互作用效应，p = 0.009）和腹部内脏脂肪（AVF：SNP效应，p = 0.007，相互作用效应，p = 0.01）。同样，TCF7L2 rs12573128单独或与膳食脂肪摄入相互作用时，会影响胰岛素敏感性（SNP效应和相互作用效应，p≤0.008）和葡萄糖耐量（SNP效应p≤0.009，相互作用效应，p≤0.01）。
这些结果表明，基因-膳食脂肪相互作用可能影响葡萄糖稳态相关表型，并在确定与T2DM易感基因相关的糖尿病风险增加中起重要作用。
