CDKAL1 (rs10946398) and TCF7L2 (rs7903146) gene polymorphisms and their association with risk of type-2 diabetes mellitus in population of Uttarakhand, India

Abstract

PurposeType 2 diabetes mellitus (T2DM), a non- insulin dependent form of diabetes is predominantly the outcome of multivariate factors ranging from genetic, hereditary to environmental factors. CDKAL1 ((rs10946398)), gene play a permissive role in β-cell function by inhibiting activity of CDK5, the decrease of insulin gene expression. TCF7L2 ((rs7903146)) gene involved in the Wnt signalling pathway, has its direct effects on glucose-induced, which may risk prevalence of T2DM. The present study aims to understand the association of CDKAL1 and TCF7L2 Gene polymorphism in T2DM patients among the population of Uttarakhand, India. Materials and methodsThe present study included 400 T2DM subjects and 400 healthy controls. DNA extraction done from blood serum collected in plain vials and CDKAL1, TCF7L2 gene polymorphism was done by the PCR-RFLP method. ResultsSignificant differences were observed in BMI (kg/m2), FPG (mg/dl), PPG (mg/dl), HbA1c, FPI, systolic BP (mmHg), diastolic BP (mmHg) among the subjects and controls (all p < .0001). Genotypes of CDKAL1 and TCF7L2 genes among T2DM and healthy controls was found to be statistically significantly (p < .0001).Among the T2DM subjects, CDKAL1 genotypes GG, GC and CC were 32.5%, 60% and 7.5% while in healthy control, CDKAL1 genotypes GG, GC and CC were 58%, 39% and 3% respectively. Among the T2DM subjects, TCF7L2 genotype CC, CT and TT were 35%, 63% and TT 2.5% while in healthy control CC, CT, TT were 53%, 46% and 1% respectively. Higher heterozygous GC genotype and mutant CC genotype. Higher C allele frequency (0.37%) noticed in patients as compare to control C allele (0.22%). Odd ratio with 95% CI were calculated for CDKAL1, GC and CC had 2.79 (2.08–3.75) and 4.13 (2.08–8.20) risk taking GG as reference and TCF7L2, CT and TT had 2.09 (1.57–2.78), 3.04 (1.01–9.09) risk taking CC in T2DM subjects. ConclusionStudy concluded that CDKAL1 heterozygous GC, mutant CC were higher in among T2DM and TCF7L2 heterozygous CT, mutant TT were higher among T2DM subjects suggested connected with T2DM. Higher odds and relative risk was found with CDKAL1, TCF7L2 heterozygous GC, CT and mutant CC, TT genotypes respectively.