A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
A variant in CDKAL1 influences insulin response and risk of type 2 diabetes
复制标题
DOI：
10.1038/ng2043
复制
发表时间：
2007-06-01
期刊：
影响因子：
30.8
通讯作者：
Stefansson, Kari
中科院分区：
文献类型：
--
作者：
Steinthorsdottir, Valgerdur;Thorleifsson, Gudmar;Stefansson, Kari
我们在冰岛病例和对照组中进行了一项2型糖尿病（T2 D）的全基因组关联研究，我们发现先前描述的转录因子7样2基因（TCF 7 L2）的变异赋予了最显著的风险。除了证实两个最近发现的风险变异（1），我们还发现了一个与欧洲血统个体T2 D相关的CDKAL 1基因变异（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 x 10（-9））和香港汉族血统的个体（OR = 1.25（1.11 ~ 1.40），P = 0.00018）。这种变异的基因型OR表明，纯合子携带者的影响明显强于杂合子携带者。在欧洲和香港组中，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%，表明该变体通过减少胰岛素分泌而赋予T2 D的风险。
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(1), 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.