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


RESULTS
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.


CONCLUSIONS
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.
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Malmoe, Sweden. Valeri.Lyssenko@med.lu.se
Valeriya
V
Lyssenko
D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D014644:Genetic Variation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D012307:Risk Factors; D012636:Secretory Rate / Q000502:physiology; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
D007328:Insulin; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D005947:Glucose