Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.
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Authors
Grant, Struan F AThorleifsson, Gudmar
Reynisdottir, Inga
Benediktsson, Rafn
Manolescu, Andrei
Sainz, Jesus
Helgason, Agnar
Stefansson, Hreinn
Emilsson, Valur
Helgadottir, Anna
Styrkarsdottir, Unnur
Magnusson, Kristinn P
Walters, G Bragi
Palsdottir, Ebba
Jonsdottir, Thorbjorg
Gudmundsdottir, Thorunn
Gylfason, Arnaldur
Saemundsdottir, Jona
Wilensky, Robert L
Reilly, Muredach P
Rader, Daniel J
Bagger, Yu
Christiansen, Claus
Gudnason, Vilmundur
Sigurdsson, Gunnar
Thorsteinsdottir, Unnur
Gulcher, Jeffrey R
Kong, Augustine
Stefansson, Kari
Issue Date
2006-03-01
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Nat. Genet. 2006, 38(3):320-3Abstract
We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q. We genotyped 228 microsatellite markers in Icelandic individuals with type 2 diabetes and controls throughout a 10.5-Mb interval on 10q. A microsatellite, DG10S478, within intron 3 of the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4) was associated with type 2 diabetes (P = 2.1 x 10(-9)). This was replicated in a Danish cohort (P = 4.8 x 10(-3)) and in a US cohort (P = 3.3 x 10(-9)). Compared with non-carriers, heterozygous and homozygous carriers of the at-risk alleles (38% and 7% of the population, respectively) have relative risks of 1.45 and 2.41. This corresponds to a population attributable risk of 21%. The TCF7L2 gene product is a high mobility group box-containing transcription factor previously implicated in blood glucose homeostasis. It is thought to act through regulation of proglucagon gene expression in enteroendocrine cells via the Wnt signaling pathway.Description
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http://dx.doi.org/10.1038/ng1732ae974a485f413a2113503eed53cd6c53
10.1038/ng1732
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