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

Diabetologia. 2007 Jan;50(1):63-7. doi: 10.1007/s00125-006-0502-2. Epub 2006 Nov 9.


Aims and hypothesis: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • India
  • Linkage Disequilibrium / genetics
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • TCF Transcription Factors / genetics*
  • TCF Transcription Factors / physiology
  • Transcription Factor 7-Like 2 Protein


  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein