Investigation of gene-diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study.
The gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have a major role in the pathophysiology of type 2 diabetes. Specific genetic and dietary factors have been found to influence the release and action of incretins. We examined the effect of interactions between seven incretin-related genetic variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary components (whey-containing dairy, cereal fibre, coffee and olive oil) on the risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study.



The current case-cohort study included 8086 incident type 2 diabetes cases and a representative subcohort of 11,035 participants (median follow-up: 12.5 years). Prentice-weighted Cox proportional hazard regression models were used to investigate the associations and interactions between the dietary factors and genes in relation to the risk of type 2 diabetes.



An interaction (p = 0.048) between TCF7L2 variants and coffee intake was apparent, with an inverse association between coffee and type 2 diabetes present among carriers of the diabetes risk allele (T) in rs12255372 (GG: HR 0.99 [95% CI 0.97, 1.02] per cup of coffee; GT: HR 0.96 [95% CI 0.93, 0.98]); and TT: HR 0.93 [95% CI 0.88, 0.98]). In addition, an interaction (p = 0.005) between an incretin-specific genetic risk score and coffee was observed, again with a stronger inverse association with coffee in carriers with more risk alleles (0-3 risk alleles: HR 0.99 [95% CI 0.94, 1.04]; 7-10 risk alleles: HR 0.95 [95% CI 0.90, 0.99]). None of these associations were statistically significant after correction for multiple testing.



Our large-scale case-cohort study provides some evidence for a possible interaction of TCF7L2 variants and an incretin-specific genetic risk score with coffee consumption in relation to the risk of type 2 diabetes. Further large-scale studies and/or meta-analyses are needed to confirm these interactions in other populations.
D000483:Alleles; D016022:Case-Control Studies; D003069:Coffee; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004032:Diet; D004043:Dietary Fiber; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D000069463:Olive Oil; D016016:Proportional Hazards Models; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics
D003069:Coffee; D004043:Dietary Fiber; D054795:Incretins; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D008565:Membrane Proteins; D000069463:Olive Oil; D058118:Transcription Factor 7-Like 2 Protein; C114987:wolframin protein; D005749:Gastric Inhibitory Polypeptide
Coffee; Dairy; Fibre; GIPR; Gene–environment interaction; Incretins; KCNQ1; Olive oil; TCF7L2; WFS1