Investigation of gene diet interactions in the incretin system and risk of type 2 diabetes: the EPIC InterAct study
Aims/hypothesisThe 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.MethodsThe 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.ResultsAn 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.Conclusions/interpretationOur 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.