Tcfl

The genome region 10q25 harbors the transcription factor 7-like 2 (TCF7L2) gene. In studies in three cohorts, it was shown that heterozygous (38%) and homozygous (7%) carriers of a prevalent intron microsatellite have relative risks of 1.4 and 2.4 for type 2 diabetes, respectively. Due to the high prevalence of this microsatellite the population-attributable risk for diabetes is around 18%. TCF7L2 is a transcription factor influencing the proglucagone gene; it is has been proposed to influence glucagon-like peptide 1 (GLP-1) levels. GLP-1 is one of the peptides encoded by this gene; it has stimulating effects both on insulin secretion per se, and on beta-cell growth (89). The importance of this gene can also be appreciated from studies showing that progression from IGT to diabetes was around 50% higher in homozygous carriers of each one of two polymorphisms in this gene (90).

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