CDKAL1基因的一个变体影响胰岛素反应及2型糖尿病风险。

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.

作者信息

Steinthorsdottir Valgerdur, Thorleifsson Gudmar, Reynisdottir Inga, Benediktsson Rafn, Jonsdottir Thorbjorg, Walters G Bragi, Styrkarsdottir Unnur, Gretarsdottir Solveig, Emilsson Valur, Ghosh Shyamali, Baker Adam, Snorradottir Steinunn, Bjarnason Hjordis, Ng Maggie C Y, Hansen Torben, Bagger Yu, Wilensky Robert L, Reilly Muredach P, Adeyemo Adebowale, Chen Yuanxiu, Zhou Jie, Gudnason Vilmundur, Chen Guanjie, Huang Hanxia, Lashley Kerrie, Doumatey Ayo, So Wing-Yee, Ma Ronald C Y, Andersen Gitte, Borch-Johnsen Knut, Jorgensen Torben, van Vliet-Ostaptchouk Jana V, Hofker Marten H, Wijmenga Cisca, Christiansen Claus, Rader Daniel J, Rotimi Charles, Gurney Mark, Chan Juliana C N, Pedersen Oluf, Sigurdsson Gunnar, Gulcher Jeffrey R, Thorsteinsdottir Unnur, Kong Augustine, Stefansson Kari

机构信息

deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.

出版信息

Nat Genet. 2007 Jun;39(6):770-5. doi: 10.1038/ng2043. Epub 2007 Apr 26.

DOI:10.1038/ng2043

PMID:17460697

Abstract

We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.

摘要

我们针对冰岛的2型糖尿病（T2D）病例和对照开展了一项全基因组关联研究，发现转录因子7样2基因（TCF7L2）中一个先前已描述的变异带来了最显著的患病风险。除了证实两个最近发现的风险变异外，我们还在欧洲血统个体（等位基因特异性比值比（OR）= 1.20（95%置信区间，1.13 - 1.27），P = 7.7×10⁻⁹）以及来自中国香港的汉族血统个体（OR = 1.25（1.11 - 1.40），P = 0.00018）中鉴定出一个与T2D相关的CDKAL1基因变异。该变异的基因型OR表明，纯合携带者的效应比杂合携带者显著更强。在欧洲和中国香港人群中，纯合子的OR分别为1.50（1.31 - 1.72）和1.55（1.23 - 1.95）。纯合子的胰岛素反应比杂合子或非携带者低约20%，这表明该变异通过降低胰岛素分泌带来T2D患病风险。