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

Diabetologia. 2016 Dec;59(12):2613-2621. doi: 10.1007/s00125-016-4090-5. Epub 2016 Sep 13.

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.

Keywords: Coffee; Dairy; Fibre; GIPR; Gene–environment interaction; Incretins; KCNQ1; Olive oil; TCF7L2; WFS1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Coffee
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diet*
  • Dietary Fiber
  • Female
  • Gastric Inhibitory Polypeptide / genetics
  • Humans
  • Incretins / metabolism*
  • KCNQ1 Potassium Channel / genetics
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Olive Oil
  • Proportional Hazards Models
  • Transcription Factor 7-Like 2 Protein / genetics

Substances

  • Coffee
  • Dietary Fiber
  • Incretins
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Membrane Proteins
  • Olive Oil
  • Transcription Factor 7-Like 2 Protein
  • wolframin protein
  • Gastric Inhibitory Polypeptide