Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.
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.
Grant
Struan F A
SF
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. struan.grant@decode.is
Thorleifsson
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Valur
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Ebba
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Thorbjorg
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Arnaldur
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Jona
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Wilensky
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Muredach P
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DJ
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Thorsteinsdottir
Unnur
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D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D015331:Cohort Studies; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D012016:Reference Values; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein
D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein