The transcription factor 7-like 2 gene and increased risk of type 2 diabetes: an update

The purpose of this review is to provide a comprehensive evaluation of the most important type 2 diabetes gene to date, transcription factor 7 like-2.

An important step to find genetic causes of type 2 diabetes in 2006 was the identification of the fact that variants in the gene encoding transcription factor 7 like-2 reproducibly increase susceptibility to type 2 diabetes in almost all populations studied. This gene has since then emerged as the most important type 2 diabetes gene. Genetic variants in transcription factor 7 like-2 confer a strong risk of type 2 diabetes possibly mediated by altering expression of transcription factor 7 like-2 in pancreatic islets. Risk variants in the transcription factor 7 like-2 influence insulin secretions both in vitro and in vivo. The risk T allele of this single nucleotide polymorphism also seems to have effects on the enteroinsular axis and the relationship between the incretin hormone glucose-dependent insulinotropic peptide and its target hormones, glucagon and insulin. Given transcription factor 7 like-2s' central role in the Wnt signaling pathway, it would be important to define whether the variant is associated with increased or decreased Wnt signaling.

The fact that transcription factor 7 like-2 is by far the strongest type 2 diabetes susceptibility gene to date emphasizes the importance of exploring the potential of manipulating this pathway in future treatment of the disease.