Abstract

Common variants of the transcription factor 7-like 2 (TCF7L2) gene have been found to be associated with type 2 diabetes in different ethnic groups. The Japanese-Brazilian population has one of the highest prevalence rates of diabetes. Therefore, the aim of the present study was to assess whether two single-nucleotide polymorphisms (SNPs) of TCF7L2, rs7903146 and rs12255372, could predict the development of glucose intolerance in Japanese-Brazilians. In a population-based 7-year prospective study, we genotyped 222 individuals (72 males and 150 females, aged 56.2 ± 10.5 years) with normal glucose tolerance at baseline. In the study population, we found that the minor allele frequency was 0.05 for SNP rs7903146 and 0.03 for SNP rs12255372. No significant allele or genotype association with glucose intolerance incidence was found for either SNP. Haplotypes were constructed with these two SNPs and three haplotypes were defined: CG (frequency: 0.94), TT (frequency = 0.027) and TG (frequency = 0.026). None of the haplotypes provided evidence for association with the incidence of glucose intolerance. Despite no associations between incidence of glucose intolerance and SNPs of the TCF7L2 gene in Japanese-Brazilians, we found that carriers of the CT genotype for rs7903146 had significantly lower insulin levels 2 h after a 75-g glucose load than carriers of the CC genotype. In conclusion, in Japanese-Brazilians, a population with a high prevalence of type 2 diabetes, common TCF7L2 variants did not make major contributions to the incidence of glucose tolerance abnormalities.

Highlights

  • Population groups with defined characteristics have been studied to assess the role of environmental and genetic factors in the etiology of non-communicable diseases such as diabetes mellitus

  • We tested for associations between incidence of glucose intolerance and single-nucleotide polymorphisms (SNPs) of the transcription factor 7-like gene (TCF7L2) gene in a cohort of Japanese-Brazilians

  • TCF7L2 variants have been consistently associated with an increased risk for type 2 diabetes in diverse populations [3,4,5,6,7,8,9,10], the present study showed that the presence of SNPs rs7903146

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Summary

Introduction

Population groups with defined characteristics have been studied to assess the role of environmental and genetic factors in the etiology of non-communicable diseases such as diabetes mellitus. In the second phase of the study, 7 years later, this prevalence had increased to 36.1%, being one of the highest worldwide [1]. This situation could be reflecting the strong genetic susceptibility of this population associated with an unfavorable environment. The single-nucleotide polymorphisms (SNPs) with the strongest correlation with DG10S478 were rs7903146, rs12255372, rs7901695, rs11196205, and rs7895340 After this initial finding many other studies have found consistent associations between TCF7L2 variants and type 2 diabetes in populations of different ethnic groups [3,4,5,6,7,8,9,10]

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