| Summary: | Aims/hypothesis: 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 interactions between 7 incretin-related genetic variants in GIPR, KCNQ1, TCF7L2 and WFS1 and dietary components (whey-containing dairy, cereal fibre, coffee, olive oil) on risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC) - InterAct study. <br/> Methods: The current case-cohort study included 8086 incident type 2 diabetes cases and a representative sub-cohort of 11,035 participants (median follow-up, 12.5 years). Prentice-weighted Cox proportional hazard regression models were used to investigate the association and interaction between the dietary factors and genes in relation to risk of type 2 diabetes. <br/> Results: An interaction (p=0.048) between TCF7L2 variants and coffee intake on type 2 diabetes risk was apparent, with an inverse association with coffee only present among carriers of the diabetes risk allele (T) in rs12255372 (GG: HR (95%CI) = 0.99 (0.97;,1.02) per cup of coffee; GT: HR (95%CI) = 0.96 (0.93;, 0.98); and TT: HR (95%CI) = 0.93 (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 between coffee and type 2 diabetes in carriers with more risk alleles (0-3 risk alleles: HR (95%CI) = 0.99 (0.94;,1.04); 7-10 risk alleles: HR (95%CI) = 0.95 (0.90;,0.99)). None of these associations was statistically significant after correction for multiple testing. <br/> Conclusions/interpretation: Our large-scale case-cohort study provides some evidence for a possible interaction between TCF7L2 variants as well as an incretin- specific genetic risk score and coffee consumption on risk of type 2 diabetes. Further large-scale studies and/or meta-analyses are needed for confirming this interaction in other populations.
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