A genome-wide association study identifies novel loci associated with susceptibility to chronic myeloid leukemia
A genome-wide association study identifies novel loci associated with susceptibility to chronic myeloid leukemia
复制标题
DOI：
10.1182/blood-2011-01-329797
复制
发表时间：
2011-06-23
期刊：
影响因子：
20.3
通讯作者：
Lipton, Jeffrey H.
中科院分区：
文献类型：
--
作者：
Kim, Dong Hwan (Dennis);Lee, Seung-Tae;Lipton, Jeffrey H.
在目前的研究中，我们使用全基因组分析确定了2个慢性粒细胞白血病（CML）易感性的遗传标记。共纳入2744例受试者（671例病例和2073例对照），其中202例韩国CML患者和497例对照受试者作为发现集入组。在第二个韩国组的237例患者和1000例对照受试者以及另一个欧洲血统的加拿大队列（包括232例患者和576例对照受试者）中验证了发现集中的显著结果。分析显示两个候选基因座6q25.1和17p11.1与CML易感性显著相关，最低组合P值分别为2.4 x 10（-6）和1.3 x 10（-12）。这些区域中的候选基因包括RMND 1、AKAP 12、ZBTB 2和WSB 1。位点6q25.1在韩国和欧洲队列中均得到验证，而17p11.1仅在韩国队列中得到验证。这些发现表明，6q25.1和17p11.1的遗传变异可能使人易于发生CML。（血。2011;117（25）：6906-6911）
In the current study, we identified 2 genetic markers for susceptibility to chronic myeloid leukemia (CML) using a genome-wide analysis. A total of 2744 subjects (671 cases and 2073 controls) were included, with 202 Korean CML patients and 497 control subjects enrolled as a discovery set. Significant findings in the discovery set were validated in a second Korean set of 237 patients and 1000 control subjects and in an additional Canadian cohort of European descent, including 232 patients and 576 control subjects. Analysis revealed significant associations of 2 candidate loci, 6q25.1 and 17p11.1, with CML susceptibility, with the lowest combined P values of 2.4 x 10(-6) and 1.3 x 10(-12), respectively. Candidate genes in those regions include RMND1, AKAP12, ZBTB2, and WSB1. The locus 6q25.1 was validated in both Korean and European cohorts, whereas 17p11.1 was validated only in the Korean cohort. These findings suggest that genetic variants of 6q25.1 and 17p11.1 may predispose one to the development of CML. (Blood. 2011;117(25):6906-6911)