IntroductionType 2 diabetes mellitus (T2DM) is one of the most challenging health problems of the 21st century. Today more than 371 million people have diabetes globally (1). This figure shows that the number of cases of diabetes is more than expected and has already reached the estimation for the year 2030 (2). Additionally, approximately 50% of people with diabetes are unaware that they have the disease. In 2012, diabetes was responsible for 4.8 million deaths, half of them under the age of 60, and 471 billion USD spent (1). The Turkish population is no exception to this trend. Understanding the mechanisms that contribute to the pathogenesis of T2DM is crucial in implementing rational treatment strategies and to prevent the increasing occurrence of diabetes. T2DM is a polygenic metabolic disorder that can occur in different age groups as a result of the interaction of genetic and environmental factors (3). To determine the genetic basis of T2DM, several genes that were predicted to be T2DM risk factors were studied in numerous populations. Contrary to expectations, many of them conferred only modest effects regarding disease risk and mostly with conflicting results (4,5). The TCF7L2 gene (also known as TCF-4) on chromosome 10q25 has the strongest association with an increased risk of T2DM, and this finding has been well-replicated in multiple populations (6-21). Reports of strong associations between TCF7L2 gene variants, especially rs7903146 T, and T2DM have been predominantly obtained from European populations. However, unlike populations of European origin, in Asian populations, either these variants are unrelated or different variants within the TCF7L2 gene are associated with disease risk (21-25). In Turkey, which is a geographic and cultural bridge between Europe and Asia, a study that investigates the association between TCF7L2 polymorphisms and T2DM is lacking. In this study, we aimed to determine whether TCF7L2 variants are major contributors to T2DM in Turkish populations. Our population comprised nonobese individuals to Background/aim: Type 2 diabetes (T2D) is a multifactorial disease, determined by environmental and genetic factors. Currently, the transcription factor 7-like 2 (TCF7L2) gene shows the strongest association with T2D. In this study, we investigated whether TCF7L2 gene polymorphisms are associated with T2D in a Turkish population.
Materials and methods:Using PCR-RFLP and PCR-SSCP, we genotyped six intronic polymorphisms in the TCF7L2 gene, commonly associated with T2D, in 169 individuals with diabetes and 119 healthy controls.
Results:We found that rs7903146 C → T substitution in intron 3 (OR: 1.9, P = 0.005) and rs12255372 G → T substitution in intron 4 (OR: 2.1, P = 0.002) were significantly associated with T2D while other SNPs were not associated (P > 0.05). We determined no association between TCF7L2 gene polymorphisms and fasting glucose, fasting insulin, HbA1c, or HOMA-IR levels (P > 0.05), except for rs7903146 C → T substitution, which was significantly associated with the fastin...