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

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, Volume 59, Issue 12, pp 2613–2621

First Online: 13 September 2016Received: 10 May 2016Accepted: 18 July 2016


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.

KeywordsCoffee Dairy Fibre Gene–environment interaction GIPR Incretins KCNQ1 Olive oil TCF7L2 WFS1 AbbreviationsCEUUtah Residents with Northern and Western European Ancestry

ENDBEPIC nutrient database

EPICEuropean Prospective Investigation into Cancer and Nutrition

GIPGlucose-dependent insulinotropic peptide

GIPRGastric inhibitory polypeptide receptor

GLP-1Glucagon-like peptide-1

GWASGenome-wide association studies

IQRInterquartile range

KCNQ1Potassium voltage-gated channel subfamily Q member 1

LDLinkage disequilibrium

SNPSingle nucleotide polymorphism

TCF7L2Transcription factor 7-like 2

WFS1Wolframin ER transmembrane glycoprotein

The InterAct Consortium list of authors is shown in the electronic supplementary material ESM.

Electronic supplementary materialThe online version of this article doi:10.1007-s00125-016-4090-5 contains peer-reviewed but unedited supplementary material, which is available to authorised users.

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Autor: The InterAct Consortium


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