The Role of TCF7L2 in Type 2 Diabetes

Diabetes. 2021 Jun;70(6):1220-1228. doi: 10.2337/db20-0573. Epub 2021 May 20.


TCF7L2 is the most potent locus for type 2 diabetes (T2D) risk and the first locus to have been robustly reported by genomic linkage studies. TCF7L2 is a transcription factor that forms a basic part of the Wnt signaling pathway. This gene has highly conserved sequence regions that correspond to functional domains. The association of TCF7L2 with T2D is one of the most powerful genetically discovered in studies of complex diseases, as it has been consistently replicated in multiple populations with diverse genetic origins. The mechanisms over which TCF7L2 exerts its effect on T2D are still not well understood. In this article, we describe the main molecular mechanisms of how TCF7L2 is related to T2D. TCF7L2 variants associated with T2D risk exert an influence on the initial therapeutic success of the hypoglycemic oral agent sulfonylurea. Thus, it is important to know whether there are other TCF7L2 variants associated with T2D that can influence treatment with oral hypoglycemic agents. Resequencing of the TCF7L2 gene in diverse ethnic groups is required to reveal common and rare variations and their role in different pathologies and in adverse reactions to drugs. Identification of TCF7L2-susceptibility disease variants will permit, at a given moment, offering of therapies to patients according to their genotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipogenesis / genetics
  • Animals
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • Transcription Factor 7-Like 2 Protein / genetics
  • Transcription Factor 7-Like 2 Protein / physiology*
  • Wnt Signaling Pathway / genetics


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