Abstract:
Rate of occurrence of non-insulin dependence diabetes mellitus (NIDDM) is burgeoning at an
alarming rate every year. Type 2 diabetes mellitus (T2DM) is a condition in which body doesn’t
respond efficiently to insulin or develops resistance against insulin. It is ascribed to both genetic
and environmental factors. The interplay of genetic and environmental factors make it difficult to
pinpoint the exact mechanism and to implicate the pancreatic beta cells for progression of diabetes.
However, there is a growing interest in involvement of genetics in pathogenesis of T2DM. This
study was conducted to ascertain association analysis of SNPs (rs 12255372 and rs 4506565) of
TCF7L2 gene with diabetes in a total of 186 subjects. For this, allele specific polymerase chain
reaction was carried out to amplify SNPs of TCF7L2 and to examine their prevalence in
population. A significant association was seen between these SNPs and T2DM. Predisposition to
diabetes increase with presence of GT genotype in rs 12255372 with OR= 2.25, 95% CI= 1.2-4.07
, P=0.003** and AT genotype in rs 4506565 with OR= 1.35, 95% CI=0.7-2.4 , P=0.002**.The
allelic distribution shows the high prevalence of risk allele T in experimental than in control.
Moreover, computational analysis was performed to analyze the underlying mechanism of
TCF7L2 SNPs and their role in increasing the susceptibility of T2DM. No significant change was
seen in splicing mechanism when observed through softwares such as Splice View, Alternate
Splice Site Predictor (ASSP), Exon Splice Enhancer (ESE). However, alteration of two motifs
(Gfi1, Gfi1b) are seen in case of rs4506565 and alteration of five motifs in case of rs12255372
when observed through HaploReg software. Another software, Ensembl Variant Effect Predictor
(VEP) has predicted rs12255372 as a risk allele and thus shows its clinical significance in
pathogenesis of T2DM.
