TY - JOUR
T1 - Investigation of gene–diet interactions in the incretin system and risk of type 2 diabetes
T2 - the EPIC-InterAct study
AU - Heraclides, Alexandros
AU - Meidtner, Karina
AU - Buijsse, Brian
AU - van der Schouw, Yvonne T.
AU - Sluijs, Ivonne
AU - van der A, Daphne L.
AU - Kuijsten, Anneleen
AU - Agudo, Antonio
AU - Ardanaz, Eva
AU - Boeing, Heiner
AU - Feskens, Edith J.M.
AU - Gavrila, Diana
AU - Katzke, Verena
AU - Key, Timothy J.
AU - Kühn, Tilman
AU - Krogh, Vittorio
AU - Kyrø, Cecilie
AU - Molina-Portillo, Elena
AU - Mortensen, Lotte Maxild
AU - Nilsson, Peter M.
AU - Overvad, Kim
AU - Palli, Domenico
AU - Panico, Salvatore
AU - Ricceri, Fulvio
AU - Tumino, Rosario
AU - Forouhi, Nita G.
AU - Langenberg, Claudia
AU - Scott, Robert
AU - Franks, Paul W.
AU - Schulze, Matthias B.
AU - Riboli, Elio
AU - Wareham, Nicholas J.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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.
AB - 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.
KW - Coffee
KW - Dairy
KW - Fibre
KW - Gene–environment interaction
KW - GIPR
KW - Incretins
KW - KCNQ1
KW - Olive oil
KW - TCF7L2
KW - WFS1
UR - https://www.scopus.com/pages/publications/84987619279
U2 - 10.1007/s00125-016-4090-5
DO - 10.1007/s00125-016-4090-5
M3 - Article
C2 - 27623947
AN - SCOPUS:84987619279
SN - 0012-186X
VL - 59
SP - 2613
EP - 2621
JO - Diabetologia
JF - Diabetologia
IS - 12
ER -