Genetic polymorphisms in TCF7L2 and PPARG genes and susceptibility to Type 2 diabetes mellitus

Abstract

Transcription factor 7-like 2 (TCF7L2) plays an important role in insulin resistance and peroxisome proliferator-activated receptor γ (PPARG) is directly targeted by antidiabetic drug. This study was designed to investigate the association of genetic variants in TCF7L2 and PPARG and T2DM susceptibility. Blood samples were collected from 472 subjects (221 controls and 251 T2DM cases) after ethical approval. All subjects were genotyped for two single nucleotide polymorphisms (SNPs) in each gene TCF7L2 (+9017G>T and -41435C>T) and PPARG (-44458C>G, -17676A>G) using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) and amplification-refractory mutation system (ARMS-PCR). The TCF7L241435C>T polymorphism showed significantly higher frequency of 'TT' genotype in controls (12.2%) (P = 0.023). Haplotype 'GC*' of TCF7L2 (+9017G>T,-41435C>T) showed significant association with T2DM (P = 0.043). We conclude that individuals with 'GTG*' allelic combination were at significantly higher risk for T2DM (OR = 5.1, P=0.0002 respectively) whereas GCG* and GTA* allelic combinations showed significant protection against T2DM.The individual SNPs in TCF7L2 and PPARG genes were non-informative in genotyping analysis but showed significant risk for T2DM when analyzed together.