Association between Transcription Factor 7-Like 2 Gene Polymorphisms rs7903146 and rs12255372 with the Risk of Diabetic Nephropathy among South Indian Population

Abstract

Abstract Introduction: Transcription factor 7-like 2 (TCF7L2) gene has been associated with the genetic predisposition of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different populations. The study aimed to explore the correlation between rs7903146 and rs12255372 polymorphisms of TCF7L2 gene and DN among the South Indian population. Methods: Polymerase chain reaction (PCR)-based direct sequencing method and allele-specific PCR were used to determine the genotypes of TCF7L2 polymorphisms in 20 normal glucose tolerance (NGT) participants, 35 T2DM patients without DN and 35 T2DM patients with DN. The differences in genotype and allelic distribution between the study groups were analyzed by Chi-square test and odds ratio (OR) with 95% confidence interval (CI) which were used to indicate the relative risk of DN. Results: The distribution of TCF7L2 gene polymorphism rs7903146 prevalence was as follows: in the NGT group, CC, 65%; CT, 30%; TT, 5%; in the T2DM without DN group, CC, 25.71%; CT, 62.86%; TT, 11.43%; and in the T2DM with DN group, CC, 31.43%; CT, 60.0%; TT, 8.57%. The distribution of rs12255372 was as follows: in the NGT group, GG, 80%; GT, 15%; TT, 5%; in the T2DM without DN group, GG, 42.86%; GT, 41.46%; TT, 8.57%; and in the T2DM with DN group, GG, 48.57%; GT, 40%; TT, 5.71%. The T allele of rs7903146 polymorphism was associated with an increased risk of T2DM without DN (OR = 3.0; 95% CI = 1.21–7.437; P = 0.010) and T2DM with DN (OR = 2.51; 95% CI = 1.00–6.252; P = 0.04), and the T allele of rs12255372 polymorphism was also associated with increased risk of T2DM without DN (OR = 3.42; 95% CI = 1.18–9.902; P = 0.018) and not with T2DM with DN when compared with NGT individuals. Conclusion: In our study, the T allele of the rs7903146 single-nucleotide polymorphism in the TCF7L2 gene confers the risk of developing DN in diabetes patients, but the T allele of the rs12255372 polymorphism in the TCF7L2 gene is associated with T2DM and its association with DN is arbitrated through T2DM.