Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes

被引：1651

作者：

Grant, SFA

Thorleifsson, G

Reynisdottir, I

Benediktsson, R

Manolescu, A

Sainz, J

Helgason, A

Stefansson, H

Emilsson, V

Helgadottir, A

Styrkarsdottir, U

Magnusson, KP

Walters, GB

Palsdottir, E

Jonsdottir, T

Gudmundsdottir, T

Gylfason, A

Saemundsdottir, J

Wilensky, RL

Reilly, MP

Rader, DJ

Bagger, Y

Christiansen, C

Gudnason, V

Sigurdsson, G

Thorsteinsdottir, U

Gulcher, JR

Kong, A

Stefansson, K

机构：

[1] deCODE Genet, IS-101 Reykjavik, Iceland

[2] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

[3] Natl Univ Hosp Reykjavik, IS-108 Reykjavik, Iceland

[4] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[5] Ctr Clin & Basic Res AS, DK-2750 Ballerup, Denmark

来源：

NATURE GENETICS | 2006年 / 38卷 / 03期

关键词：

D O I：

10.1038/ng1732

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We have previously reported suggestive linkage of type 2 diabetes mellitus to chromosome 10q(1). 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(2).

引用

页码：320 / 323

页数：4

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