title: Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes.
abstract: 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.
authors.affiliation: deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. struan.grant@decode.is
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Inga
authors.initials: I
authors.lastname: Reynisdottir
authors.forename: Rafn
authors.initials: R
authors.lastname: Benediktsson
authors.forename: Andrei
authors.initials: A
authors.lastname: Manolescu
authors.forename: Jesus
authors.initials: J
authors.lastname: Sainz
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.forename: Valur
authors.initials: V
authors.lastname: Emilsson
authors.forename: Anna
authors.initials: A
authors.lastname: Helgadottir
authors.forename: Unnur
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: Kristinn P
authors.initials: KP
authors.lastname: Magnusson
authors.forename: G Bragi
authors.initials: GB
authors.lastname: Walters
authors.forename: Ebba
authors.initials: E
authors.lastname: Palsdottir
authors.forename: Thorbjorg
authors.initials: T
authors.lastname: Jonsdottir
authors.forename: Thorunn
authors.initials: T
authors.lastname: Gudmundsdottir
authors.forename: Arnaldur
authors.initials: A
authors.lastname: Gylfason
authors.forename: Jona
authors.initials: J
authors.lastname: Saemundsdottir
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wilensky
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Yu
authors.initials: Y
authors.lastname: Bagger
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sigurdsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gulcher
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: 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
chemical_list: D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein