The Role of <i>TCF7L2</i> in Type 2 Diabetes.

Abstract

<i>TCF7L2</i> 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 <i>TCF7L2</i> 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 <i>TCF7L2</i> is related to T2D. <i>TCF7L2</i> 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 <i>TCF7L2</i> variants associated with T2D that can influence treatment with oral hypoglycemic agents. Resequencing of the <i>TCF7L2</i> 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 <i>TCF7L2</i>-susceptibility disease variants will permit, at a given moment, offering of therapies to patients according to their genotype.