title: Whole-grain consumption and transcription factor-7-like 2 ( TCF7L2) rs7903146: gene-diet interaction in modulating type 2 diabetes risk.
abstract: Whole grains are known to influence postprandial glucose response and insulin demand and are inversely associated with diabetes risk. Genetic variation of the transcription factor-7-like 2 encoding gene (TCF7L2) is assumed to promote an early insulin secretory defect and has been consistently attributed to the risk of developing type 2 diabetes. The present study examined the hypothesis that the protective effect of whole grains might be attenuated in the presence of the rs7903146 risk-conferring T-allele. We employed a case-cohort study of 2318 randomised individuals and 724 incident type 2 diabetes cases from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Multivariate Cox regression was used to estimate relative risks of diabetes including product terms testing for the genotype-specific effect modification of dietary whole grain. Dietary intake of whole grains was assessed by a validated FFQ. The TCF7L2 rs7903146 T-allele was associated with type 2 diabetes (hazard ratio=1.51; 95 % CI 1.21, 1.87) and modified the inverse association between whole-grain intake and diabetes risk (P=0.016 for interaction). While whole-grain intake was inversely associated with diabetes risk among rs7903146 CC homozygote carriers (hazard ratio for 50 g portion per d=0.86; 95 % CI 0.75, 0.99), the T-allele negated the protective effect of whole-grain intake (hazard ratio among T-allele carriers for 50 g portion per d=1.08; 95 % CI 0.96, 1.23). These data provide evidence that the beneficial effect of whole-grain intake on diabetes risk is modified by TCF7L2 rs7903146.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. fisher@dife.de
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Frank
authors.initials: F
authors.lastname: Doering
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Schulze
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000235:genetics*; D004032:Diet; D002523:Edible Grain; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012306:Risk; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
chemical_list: D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein