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 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. Methods: 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. Results: 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. Conclusions/interpretation: 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.

Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes: the EPIC-InterAct study

Ricceri F.;
2016

Abstract

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 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. Methods: 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. Results: 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. Conclusions/interpretation: 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.
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Coffee; Dairy; Fibre; Gene–environment interaction; GIPR; Incretins; KCNQ1; Olive oil; TCF7L2; WFS1; Alleles; Case-Control Studies; Coffee; Diabetes Mellitus, Type 2; Dietary Fiber; Female; Gastric Inhibitory Polypeptide; Humans; Incretins; KCNQ1 Potassium Channel; Male; Membrane Proteins; Middle Aged; Olive Oil; Proportional Hazards Models; Transcription Factor 7-Like 2 Protein; Diet
Heraclides A.; Meidtner K.; Buijsse B.; van der Schouw Y.T.; Sluijs I.; van der A D.L.; Kuijsten A.; Agudo A.; Ardanaz E.; Boeing H.; Feskens E.J.M.; Gavrila D.; Katzke V.; Key T.J.; Kuhn T.; Krogh V.; Kyro C.; Molina-Portillo E.; Mortensen L.M.; Nilsson P.M.; Overvad K.; Palli D.; Panico S.; Ricceri F.; Tumino R.; Forouhi N.G.; Langenberg C.; Scott R.; Franks P.W.; Schulze M.B.; Riboli E.; Wareham N.J.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1766558
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