Cell free TCF7L2 gene alteration and their association with Type 2 diabetes mellitus in North Indian population

Abstract

TCF7L2 gene codes for transcription factor (TF) expressed in many human tissues such as fat, liver as well as in pancreatic islets of Langerhans. TCF7L2 involved in Wnt signalling pathway and strong connection of single nucleotide polymorphisms in the TCF7L2 gene associated with type 2 diabetes mellitus (T2DM). Present study aimed to study the clinical importance of TCF7L2 gene polymorphism and mRNA expression in T2DM patients. Present case control study included 100 T2DM cases and 100 control subjects. Study evaluate the TCF7L2 (rs7901695) gene polymorphism and their association with mRNA expression in T2DM patients. Allele specific PCR method was used to study polymorphism and quantitative real time PCR was used for expression study. All the statistical analysis was done by SPSS 21.0 software. Present study revealed that the significant differences in TCF7L2 genotype distribution among T2DM cases and healthy controls was observed (p 〈00001). Rare allele frequency distribution was observed to be high in patients (0.45) compared to healthy control (0.14). Increased risk was found to be associated with mutant homozygous CC genotype; the odds ratio was 31.93 (3.66–2.78) while heterozygous TC showed 13.51(6.70–27.21). TCF7L2 mRNA expression was found to be significantly associated with different TCF7L2 genotypes, wild type TT genotype showed 3.37-fold mRNA expression, heterozygous TC genotype showed 5.67-fold mRNA expression and mutant CC genotype showed 6.62-fold mRNA expression and difference among them was found to be significant (TT vs TC ≤0.0001; TT vs CC = 0.0002). Present study concluded that TCF7L2 heterozygosity and mutant genotype was associated with increased risk of T2DM. Increased TCF7L2 mRNA expression may be associated with worseness of disease and obesity, alcoholism may increase the severity of T2DM in North Indian population.