Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population

Diabetologia. 2008 Nov;51(11):1993-7. doi: 10.1007/s00125-008-1129-2. Epub 2008 Aug 19.


Aims/hypothesis: The gene encoding transcription factor 7-like 2 (TCF7L2) has been related to type 2 diabetes in multiple ethnic groups. Here, we investigate whether three single nucleotide polymorphisms (SNPs) in the TCF7L2 gene are associated with an impaired proinsulin:insulin ratio.

Methods: In this study we examined the associations between SNPs rs7901695, rs7903146 and rs12255372 in the TCF7L2 gene and metabolic variables affecting type 2 diabetes in a population-based study of 706 unrelated individuals (47% men and 53% women; aged 35-74 years) from the province of Segovia in central Spain (Castille), including 180 individuals with type 2 diabetes.

Results: The minor allele frequency of rs7901695, rs7903146 and rs12255372 was significantly higher in diabetic patients compared with that in non-diabetic individuals. The T (minor) allele of the variant rs7903146 was significantly associated with a greater OR for type 2 diabetes adjusted for age, sex and BMI in logistic regression analysis: OR 1.29 (95% CI 1.06-1.57, p = 0.01). This risk allele was also associated with an increased proinsulin:insulin ratio after OGTT. Similar results were obtained for the other TCF7L2 SNPs.

Conclusions/interpretation: Our results provide further evidence supporting the belief that the TCF7L2 gene is a major determinant of type 2 diabetes risk in Spain, as in other southern European populations. The association with increased proinsulin:insulin ratio after an OGTT suggests that TCF7L2 might be involved in insulin synthesis and processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Pressure
  • Body Mass Index
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Ethnic Groups
  • Fasting
  • Female
  • Genetic Variation*
  • Humans
  • Insulin / blood*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Proinsulin / blood*
  • Regression Analysis
  • Risk Factors
  • Spain
  • TCF Transcription Factors / genetics*
  • Transcription Factor 7-Like 2 Protein


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