Abstract
We attempt to evaluate the nature of association of TCF7L2 gene variants with T2DM, for the first time in the population of Hyderabad, which is considered to be diabetic capital of India. It is a case-control study of the three SNPs of TCF7L2, rs7903146, rs12255372 and rs11196205, genotyped on Sequenom Massarray platform, in a sample of 758 patients and 621 controls. The risk allele frequency of the three SNPs was found to be significantly higher in the T2DM cases than controls, implicating susceptibility for diabetes (p<0.01). The greatest risk of developing the disease was conferred by rs7903146. Further, the logistic regression of genotypes of each SNP under log additive model, and the haplotypes constituted by at least one of the three risk alleles also show significantly greater risk of developing T2DM when compared to the wild type haplotype. Further, BMI and WHR emerge as significant covariates with confounding effects. The strong association of the TCF7L2 SNPs with T2DM is consistent with the findings among other Indian and Non-Indian populations, suggesting universal phenomena of its association across ethnic groups globally, both within and outside the Indian subcontinent, albeit the functional relevance of these SNPs needs yet to be established.
Highlights
Type 2 diabetes mellitus (T2DM) is the most common form of diabetes characterized by hyperglycemia, which is caused by impairment in both insulin secretion and action
TCF7L2 gene which spans about 215.9 Kb with 17 exons is a high mobility group box containing transcription factor involved in the Wnt signaling pathway, playing a key role in cell development and regulatory mechanisms
WNT activity is important for lipid and glucose metabolism, pancreatic beta cell proliferation and function and for production of incretin hormone glucagon like peptide-1 (GLP-1) [49]
Summary
Type 2 diabetes mellitus (T2DM) is the most common form of diabetes characterized by hyperglycemia, which is caused by impairment in both insulin secretion and action. It is a chronic disease leading to various complications such as coronary heart disease, diabetic nephropathy, neuropathy and retinopathy. It is becoming an epidemic with increasing prevalence throughout the world. Unique in genetic pre-disposition of its population to diabetes, coupled with rapid urbanization, India is one of the leading countries presenting with largest number of diabetics (62.4 million). This number is increasing at an alarming rate and expected to touch 100 million by the year 2030 [1,2]. The three TCF7L2 SNPs (rs7390146, rs12255372 and rs11196205) that were strongly associated with T2DM in the above study were subsequently replicated, along with other SNPs of TCF7L2, in a huge meta-analysis [4] prompting their inclusion in any future replication effort
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