Common single nucleotide polymorphisms in TCF7L2 are reproducibly associated with type 2 diabetes and reduce the insulin response to glucose in nondiabetic individuals

被引：304

作者：

Saxena, Richa

Gianniny, Lauren

Burtt, Noel P.

Lyssenko, Valeriya

Giuducci, Candace

Sjogren, Marketa

Florez, Jose C.

Almgren, Peter

Isomaa, Bo

Orho-Melander, Marju

Lindblad, Ulf

Daly, Mark J.

Tuomi, Tiinamaija

Hirschhorn, Joel N.

Ardlie, Kristin G.

Groop, Leif C.

Altshuler, David

机构：

[1] MIT, Cambridge, MA 02139 USA

[2] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[5] Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden

[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[7] Univ Helsinki, Cent Hosp, Dept Med, Folkhalsan Inst Genet,Folkhalsan Res Ctr, Helsinki, Finland

[8] Univ Helsinki, Res Program Mol Med, Helsinki, Finland

[9] Skaraborg Inst, Skovde, Sweden

[10] Childrens Hosp, Div Genet, Boston, MA 02115 USA

[11] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA

[12] Gen Collaborat, Cambridge, MA USA

来源：

DIABETES | 2006年 / 55卷 / 10期

关键词：

LARGE-SCALE ASSOCIATION; HAPLOTYPE STRUCTURE; E23K VARIANT; GENE REGION; RISK; CHANNEL; RECEPTOR; DISEASE; CONFIRM; MAP;

D O I：

10.2337/db06-0381

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recently, common noncoding variants in the TCF7L2 gene were strongly associated with increased risk of type 2 diabetes in samples from Iceland, Denmark, and the U.S. We genotyped 13 single nucleotide polymorphisms (SNPs) across TCF7L2 in 8,310 individuals in family-based and case-control designs from Scandinavia, Poland, and the U.S. We convincingly confirmed the previous association of TCF7L2 SNPs with the risk of type 2 diabetes (rs7903146T odds ratio 1.40 [95% CI 1.30-1.50], P = 6.74 x 10(-20)). In nondiabetic individuals, the risk genotypes were associated with a substantial reduction in the insulinogenic index derived from an oral glucose tolerance test (risk allele homozygotes have half the insulin response to glucose of noncarriers, P = 0.003) but not with increased insulin resistance. These results suggest that TCF7L2 variants may act through insulin secretion to increase the risk of type 2 diabetes.

引用

页码：2890 / 2895

页数：6

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