Assessment of TCF7L2 expression after bariatric surgery.

OBJECTIVE: To assess the influence of bariatric surgery on transcription factor 7-like 2 (TCF7L2) expression and its association with body mass index (BMI) and Type 2 diabetes mellitus (T2DM). METHODS: Prospective study performed between 2016 and 2018, where 26 obese patients undergoing bariatric surgery were divided into two subgroups: diabetics and non-diabetics. The RNAs were extracted from peripheral blood samples that were obtained from each patient in two different moments: before surgery and after 12 months of follow-up. The relative expression of TCF7L2 was determined according to the delta-Ct method. RESULTS: The linear regression model of BMI x delta-Ct showed a positive correlation (p = 0.037). In the subgroups, an inversely proportional relationship was found between delta-Ct and BMI in the diabetic group and a directly proportional relationship in the non-diabetic group (p>0.05 in both). In the postoperative period, the regression model was similar to the preoperative, except when analyzing the subgroups, where diabetic patients showed a directly proportional relationship (p>0.05). The relative expression of TCF7L2 showed an average of 1.16 ± 0.91, CI-95% 0.79-1.53. There was an increase in relative expression of 48% in the non-diabetic group (p = 0.021), and a decrease of 27% in the T2DM group (p>0.05) in the postoperative. There was a positive correlation between a greater decrease in BMI and increased relative expression (p = 0.027). CONCLUSION: Our results showed that generally, the TCF7L2 expression increase with a decrease in BMI, however, for patients with T2DM, it exhibits an inverse pattern, which is normalized one year after bariatric surgery.

Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores.

Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED participants at baseline and longitudinally (8.7 years maximum follow-up). Obesity significantly interacted with the TCF7L2-rs7903146 on T2D prevalence, associations being greater in non-obese subjects. Accordingly, we prospectively observed in non-T2D subjects (n = 3607) that its association with T2D incidence was stronger in non-obese (HR: 1.81; 95% CI: 1.13-2.92, p = 0.013 for TT versus CC) than in obese subjects (HR: 1.01; 95% CI: 0.61-1.66; p = 0.979; p-interaction = 0.048). Accordingly, TCF7L2-PV was higher in non-obese subjects. Additionally, we created obesity-specific GRS with ten T2D-polymorphisms and demonstrated for the first time their higher strata-specific PV. In conclusion, we provide strong evidence supporting the need for considering obesity when analyzing the TCF7L2 effects and propose the use of obesity-specific GRS for T2D.

Association of fibrillin-3 and transcription factor-7-like 2 gene variants with metabolic phenotypes in PCOS.

Polycystic ovary syndrome (PCOS) is a complex genetic disease characterized by heritable reproductive and metabolic abnormalities. Genetic variants associated with the reproductive phenotype have been mapped to the fibrillin-3 (FBN3) gene and to a novel transcription factor-7-like 2 (TCF7L2) locus (rs11196236 G). The association of these genetic variants with metabolic phenotypes was investigated in 31 PCOS and 18 control women of European ancestry. The insulinogenic index during an oral glucose tolerance test (ΔI30/ΔG30) and insulin secretion rates at the maximal dose during a graded-glucose infusion (ISRmax) were used as indexes of insulin secretion. Endogenous glucose production (EGP) and insulin sensitivity (M/I) were determined during a euglycemic clamp. The disposition index (DI) was calculated using M/I and ΔI30/ΔG30 or ISRmax. Compared with noncarriers (n = 10) and control (n = 10), M/I was decreased (P = 1.1 × 10(-5)) in heterozygous and homozygous PCOS carriers (n = 14) of rs11196236 G and this variant predicted M/I (partial r(2) = 0.34, P = 0.005) in a regression analysis. Postabsorptive EGP tended to be higher (P = 0.040) in heterozygous and homozygous PCOS carriers of the FBN3-associated allele (n = 12), allele 8 of D19S884 (FBN3(+)), compared to PCOS noncarriers (n = 19). PCOS carriers of the rs12255372 T (TCF7L2 Caucasian type 2 diabetes mellitus (T2D) locus) had no significant associated metabolic phenotypes. We conclude that rs11196236 G TCF7L2 variant is associated with peripheral insulin resistance in PCOS but this effect is not seen in control women. The FBN3 risk allele may be associated with changes in basal glucose homeostasis in PCOS. These findings require replication in additional PCOS cohorts.