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

Investigation of Gene-Diet Interactions in the Incretin System and Risk of Type 2 Diabetes: The EPIC-InterAct Study

Free PMC article

Investigation of Gene-Diet Interactions in the Incretin System and Risk of Type 2 Diabetes: The EPIC-InterAct Study

InterAct Consortium. Diabetologia. .
Free PMC article

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.

Conflict of interest statement

Duality of interest

The authors declare that there is no duality of interest associated with this manuscript.

Contribution statement

AH conceptualised the project and wrote up the aims, specific objectives and initial analysis plan. AH was responsible for writing up the introduction and discussion sections of the manuscript. KM conducted the statistical analysis, made amendments to the analysis plan and prepared the study results. KM was responsible for writing up the methods and results sections of the manuscript. Both AH and KM had access to all data for this study and take responsibility for the manuscript contents. All authors qualify for authorship. They have all contributed to the conception and design of the study, interpretation of the data, critical revision of the article for important intellectual content and final approval of the version to be published.

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References

    1. Holst JJ, Vilsboll T, Deacon CF. The incretin system and its role in type 2 diabetes mellitus. Mol Cell Endocrinol. 2009;297:127–136. doi: 10.1016/j.mce.2008.08.012. - DOI - PubMed
    1. Saxena R, Hivert MF, Langenberg C, et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet. 2010;42:142–148. doi: 10.1038/ng.521. - DOI - PMC - PubMed
    1. Mussig K, Staiger H, Machicao F, Haring HU, Fritsche A. Genetic variants affecting incretin sensitivity and incretin secretion. Diabetologia. 2010;53:2289–2297. doi: 10.1007/s00125-010-1876-8. - DOI - PubMed
    1. Liu Z, Habener JF. Glucagon-like peptide-1 activation of TCF7L2-dependent Wnt signaling enhances pancreatic beta cell proliferation. J Biol Chem. 2008;283:8723–8735. doi: 10.1074/jbc.M706105200. - DOI - PMC - PubMed
    1. Loder MK, da Silva Xavier G, McDonald A, Rutter GA. TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic beta-cells. Biochem Soc Trans. 2008;36:357–359. doi: 10.1042/BST0360357. - DOI - PubMed

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