Genetic Association of a Polymorphic Variant (rs7903146) in TCF7L2 Gene by Allele-Specific Genotyping to Predict the Susceptibility of T2DM

Abstract

In type 2 diabetes mellitus (T2DM), transcription factor 7- like 2 (TCF7L2) gene has been linked its suscept-ibility in multiple ethnicities. This case-control study investigates the possible role of TCF7L2 variant; rs7903146 (C/T) along with anthropometric data and clinical profiles in the North Indian population. TCF7L2 polymorphism was genotyped by allele-specific PCR assay. Odds ratio (OR) and 95% Confidence Intervals were used to assess the strength of genetic association. A total of 500 human subjects consisting of 250 T2DM patients together with 250 normoglycemic controls from the region of North India. Out of total T2DM subjects, 64.4% had a family history and 74% were reported to be hypertensive. Most of the anthropometric markers showed a statistically significant (p<0.0001) association with T2DM when compared to normoglycemic controls, specifically in fasting glucose, postprandial glucose, and HbA1c. Further analysis indicates that recessive genetic model of association established that the unadjusted odds ratio of risk homozygous (TT) subjects was 2.6 fold higher (OR=2.63; 95% CI=1.27-5.43) compared to wild homozygous (CC) subjects. Simultaneously, when adjusted with age, sex, and BMI, this risk was increased up to 3.4 fold (OR=3.46; 95% CI=1.63-7.34). Risk alleles (TT subjects) were also found to be statistically significant in BMI and blood sugar parameters. This SNP was also showed significant statistical association with T2DM under dominant and co-dominant models of logistic regression even after adjusting the covariates. This study exposed the positive genetic association of the risk variant rs7903146 (T) SNP of TCF7L2 in T2DM subjects of the North India.

Keywords: rs7903146, Single nucleotide polymorphism, TCF7L2, Type 2 Diabetes Mellitus (T2DM).

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