Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Hyperglycemia in an Adult Italian Population-Based Cohort

Abstract

OBJECTIVETo assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control.RESEARCH DESIGN AND METHODSMetabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort.RESULTSAt baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for β-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow-up, fasting glucose and HOMA-B index were increased and reduced, respectively, in carriers of the T-allele. Incident impaired fasting glucose (IFG) and incident diabetes were 5.7, 10.7, 16.9% and 1.6, 1.7, 3.0% in the CC, CT, and TT genotypes, respectively. In a multiple logistic regression model, the association between incident IFG and the T-allele was significant (odds ratio [OR] 2.08 [95% CI 1.35–3.20] and 3.56 [2.11–5.98] in CT and TT genotypes, respectively).CONCLUSIONSThe T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up.

Associations of common variants in the SLC16A11 , TCF7L2, and ABCA1 genes with pediatric-onset type 2 diabetes and related glycemic traits in families: A case-control and case-parent trio study

“…Other researchers have observed similar results for these and other glycemic and insulin traits 15,[41][42][43][44][45][46][47][48][49][50] and have also observed them in children. 51 The findings regarding β-cell function in individuals without T2D might be explained by the involvement of the TCF7L2 gene in the entero-insular axis, islet gene expression, and insulin secretion, 52 and although this gene does not increase the risk of obesity, its effect on T2D can be modulated by the BMI.…”

“…In individuals without diabetes, we found that rs12255372 in the TCF7L2 gene was associated with higher fasting glucose levels ( β = 2.05, P = .039) and less HOMA‐B ( β = −32.14, P = .025), independent of age, sex, and the presence of overweight or obesity. Other researchers have observed similar results for these and other glycemic and insulin traits and have also observed them in children . The findings regarding β‐cell function in individuals without T2D might be explained by the involvement of the TCF7L2 gene in the entero‐insular axis, islet gene expression, and insulin secretion, and although this gene does not increase the risk of obesity, its effect on T2D can be modulated by the BMI .…”

Polymorphism of Transcription Factor 7-Like 2 Gene and HOMA-β Level of Individuals With and Without Type 2 Diabetes Mellitus Family History

“…The same results were reported at Arabian population (Alsmadi et al, 2008) and Indian Pima population (Guo et al, 2007) that rs7903146 has low risk to type 2 DM (OR=1.04). In another study conducted in France population (Moczulski et al, 2007) and Italian population (Gambino et al, 2010) were reported different result that rs7903146 was a risk factor of type 2 DM.…”

The rs553668 polymorphism of the ADRA2A gene predicts the worsening of fasting glucose values in a cohort of subjects without diabetes. A population‐based study

“…Incidence of impaired fasting glucose and diabetes was almost twofold higher in homozygous carriers of the A allele. The results did not change significantly after adjusting for the genotype for TCF7L2 rs7903146, which is located 1.9 Mb downstream of ADRA2A [3] and which is the strongest candidate gene for Type 2 diabetes [6,8].…”