Journal Article

Common variants in the TCF7L2 gene are strongly associated with type 2 diabetes mellitus in the Indian population

Yajnik, C. S., Frayling, T. M., Janipalli, C. S., Hattersley, A. T., Chandak, G. R., Kulkarni, S. R., Mohankrishna, P., Bhaskar, S.

2007

Overview

India has the greatest number of diabetic subjects in any one country, but the genetic basis of type 2 diabetes mellitus in India is poorly understood. Common non-coding variants in the transcription factor 7-like 2 gene (TCF7L2) have recently been strongly associated with increased risk of type 2 diabetes in European populations. We investigated whether TCF7L2 variants are also associated with type 2 diabetes mellitus in the Indian population. We genotyped type 2 diabetes patients (n = 955) and ethnically matched control subjects (n = 399) by sequencing three single nucleotide polymorphisms (SNPs) (rs7903146, rs12255372 and rs4506565) in TCF7L2. We observed a strong association with all the polymorphisms, including rs12255372 (odds ratio [OR] 1.50 [95% CI = 1.24-1.82], p = 4.0 x 10(-5)), rs4506565 (OR 1.48 [95% CI = 1.24-1.77], p = 2.0 x 10(-5)) and rs7903146 (OR 1.46 [95% CI = 1.22-1.75], p = 3.0 x 10(-5)). All three variants showed increased relative risk when homozygous rather than heterozygous, with the strongest risk for rs12255372 (OR 2.28 [95% CI = 1.40-3.72] vs OR 1.43 [95% CI = 1.11-1.83]). We found no association of the TCF7L2 genotypes with age at diagnosis, BMI or WHR, but the risk genotype at rs12255372 was associated with higher fasting plasma glucose (p = 0.001), higher 2-h plasma glucose (p = 0.0002) and higher homeostasis model assessment of insulin resistance (HOMA-R; p = 0.012) in non-diabetic subjects. Our study in Indian subjects replicates the strong association of TCF7L2 variants with type 2 diabetes in other populations. It also provides evidence that variations in TCF7L2 may play a crucial role in the pathogenesis of type 2 diabetes by influencing both insulin secretion and insulin resistance. TCF7L2 is an important gene for determining susceptibility to type 2 diabetes mellitus and it transgresses the boundaries of ethnicity.

• Publisher: Springer,Springer Nature B.V
• Subject: Adult / Alleles / Biological and medical sciences / Body mass index / Case-Control Studies / Diabetes / Diabetes Mellitus, Type 2 - ethnology / Diabetes Mellitus, Type 2 - genetics / Diabetes. Impaired glucose tolerance / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Ethnicity / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Genetic Predisposition to Disease / Genotype / Glucose / Homeostasis / Humans / India / Insulin resistance / Linkage Disequilibrium - genetics / Male / Medical sciences / Middle Aged / Odds Ratio / Plasma / Polymorphism / Polymorphism, Single Nucleotide - genetics / Research centers / Risk Factors / TCF Transcription Factors - genetics / TCF Transcription Factors - physiology / Transcription Factor 7-Like 2 Protein / Transcription factors