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

被引：20
作者：
Heraclides A. [1 ,2 ,33 ]
Meidtner K. [1 ,3 ,33 ,34 ]
Buijsse B. [4 ,11 ]
van der Schouw Y.T. [5 ,6 ]
Sluijs I. [5 ,6 ]
van der A D.L. [7 ]
Kuijsten A. [8 ,12 ]
Agudo A. [9 ]
Ardanaz E. [10 ]
Boeing H. [4 ,11 ]
Feskens E.J.M. [8 ,12 ]
Gavrila D. [13 ,14 ]
Katzke V. [15 ,17 ]
Key T.J. [16 ]
Kühn T. [15 ,17 ]
Krogh V. [18 ]
Kyrø C. [19 ]
Molina-Portillo E. [20 ]
Mortensen L.M. [21 ,22 ]
Nilsson P.M. [23 ,32 ]
Overvad K. [24 ]
Palli D. [25 ]
Panico S. [26 ]
Ricceri F. [27 ,28 ]
Tumino R. [29 ]
Forouhi N.G. [30 ,36 ]
Langenberg C. [30 ,36 ]
Scott R. [30 ,36 ]
Franks P.W. [23 ,31 ,32 ]
Schulze M.B. [1 ,33 ,34 ]
Riboli E. [35 ]
Wareham N.J. [30 ,36 ]
机构：
[1] Univ Nicosia, Sch Med, Ctr Primary Care & Populat Hlth, 21 Ilia Papakyriakou,POB 24005, CY-1700 Nicosia, Cyprus
来源：
DIABETOLOGIA | 2016年 / 59卷 / 12期
基金：
瑞典研究理事会; 荷兰研究理事会; 英国医学研究理事会;
关键词：
Coffee; Dairy; Fibre; Gene-environment interaction; GIPR; Incretins; KCNQ1; Olive oil; TCF7L2; WFS1; GASTROINTESTINAL HORMONE-SECRETION; POSTPRANDIAL LIPEMIA; GLUCOSE-TOLERANCE; INSULIN-SECRETION; FASTING GLUCOSE; TCF7L2; SUSCEPTIBILITY; RESPONSES; VARIANTS; PROTEIN;
D O I：
10.1007/s00125-016-4090-5
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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. 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. 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. 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.
引用
收藏
页码：2613 / 2621
页数：9
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