Whole-grain consumption and transcription factor-7-like 2 (TCF7L2) rs7903146: gene–diet interaction in modulating type 2 diabetes risk

Abstract

Whole grains are known to influence postprandial glucose response and insulin demand and are inversely associated with diabetes risk. Genetic variation of the transcription factor-7-like 2 encoding gene (TCF7L2) is assumed to promote an early insulin secretory defect and has been consistently attributed to the risk of developing type 2 diabetes. The present study examined the hypothesis that the protective effect of whole grains might be attenuated in the presence of the rs7903146 risk-conferring T-allele. We employed a case -cohort study of 2318 randomised individuals and 724 incident type 2 diabetes cases from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Multivariate Cox regression was used to estimate relative risks of diabetes including product terms testing for the genotype-specific effect modification of dietary whole grain. Dietary intake of whole grains was assessed by a validated FFQ. The TCF7L2 rs7903146 T-allele was associated with type 2 diabetes (hazard ratio ¼ 1·51; 95 % CI 1·21, 1·87) and modified the inverse association between whole-grain intake and diabetes risk (P¼ 0·016 for interaction). While whole-grain intake was inversely associated with diabetes risk among rs7903146 CC homozygote carriers (hazard ratio for 50 g portion per d ¼ 0·86; 95 % CI 0·75, 0·99), the T-allele negated the protective effect of whole-grain intake (hazard ratio among T-allele carriers for 50 g portion per d ¼ 1·08; 95 % CI 0·96, 1·23). These data provide evidence that the beneficial effect of whole-grain intake on diabetes risk is modified by TCF7L2 rs7903146.

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

“…While this is the case in other population groups, some studies reported a weak 33,34 or no association [35][36][37][38] . Other studies highlighted the effect of the TCF7L2 polymorphisms on the progression of T2DM 35,39 , in some ethnic population groups these variants were associated with responses to medication 40,41 , and in others their effect on the disease was modulated by the type of diet [42][43][44] .Our results [1.43 (1.00 to 2.04), p= 0.053] are comparable to those reported for other African ethnic population groups 17,18,20 . It is possible that TCF7L2 polymorphisms have different effects in various ethnic population groups depending on the diet.…”

Use of genomic panels to determine risk of developing type 2 diabetes in the general population: a targeted evidence-based review

“…Clinical scenario 1: cumulative effect of multiple genomic markers and T2D. The EPIC-Potsdam study 8 was a prospective case-cohort design with 773 individuals with T2D and 2,225 randomly selected population-based controls followed for an average of 7.1 years ( Table 3). The risk of developing T2D was associated with the TCF7L2 T allele (hazard ratio: 1.51) and was compared with daily consumption of whole grains stratified by TCF7L2 genotype.…”

“…The NUGENOB study 9 was a multicenter randomized openlabel trial that compared the benefits of two dietary interventions 8 with intermediate outcomes relevant to T2D. Only the surrogate outcome of plasma fasting glucose is relevant to this review.…”

“…Randomized trials have demonstrated that changing lifestyle factors (e.g., weight loss, improved diet, and increased physical activity) can help prevent or delay the development of diabetes. [2][3][4][5][6][7][8][9] A family history of diabetes is a major risk factor for the disease and is often included in tools designed to quantify the risk of diabetes, 10 with odds ratios (ORs) of two to six, if one or more first-degree relatives have been diagnosed with T2D. 11 A long-term study reported that the cumulative prevalence of T2D at 80 years of age is approximately 3.5 times higher (38% vs. 11%) for individuals with a first-degree relative diagnosed with T2D as compared with individuals without any relatives diagnosed with T2D.…”

Recommendations from the EGAPP Working Group: does genomic profiling to assess type 2 diabetes risk improve health outcomes?

“…Given that randomized trials have demonstrated that changing lifestyle factors (e.g., weight loss, improved diet, and increased physical activity) can result in decreased risk for diabetes, the possible knowledge of an individual's T2D increased risk by genetic testing could improve overall health outcomes. [8][9][10][11][12][13][14][15] descriptions of tests and intended use claims Four companies offering five genomic tests for T2D were identified in July 2010, and any update to the panels was verified in July 2012. The test panels included between 1 and 28 genes ( Table 1) on one or more panels.…”