Current Diabetes Reports

, 8:149

TCF7L2 genetic defect and type 2 diabetes

Article

Abstract

After two decades of limited success, the genetic architecture of type 2 diabetes (T2D) is finally being revealed. Within only 2 years, an avalanche of studies identified several genes expressed in pancreatic β cells and involved in the control of insulin secretion, such as transcription factor 7-like 2 (TCF7L2), a key element of the Wnt signaling pathway. In Europeans, genome-wide association scans showed that TCF7L2 has been the most important locus predisposing to T2D so far. For the first time, a gene is consistently involved in T2D susceptibility in all major ethnic groups. At the individual level, carrying the TCF7L2 risk allele increases T2D risk 50%. However, at the population level, the attributable risk is lower than 25% and varies with the allele frequency. The presence of the TCF7L2 rs7903146 risk allele increases TCF7L2 gene expression in β cells, possibly impairing glucagon-like peptide-1-induced insulin secretion and/or the production of new mature β cells. The tremendous association of TCF7L2 polymorphisms with T2D provides new insights into future genetic predisposition tests but remains the tip of the T2D genetic iceberg.

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Copyright information

© Current Medicine Group LLC 2008

Authors and Affiliations

  1. 1.Imperial College, Section of Genomic Medicine, Imperial College LondonHammersmith HospitalLondonUK

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