Jiang Danjie, Li Yirun, Hong Qingxiao, Shen Yusheng, Xu Chunjing, Xu Yan, Zhu Huangkai, Dai Dongjun, Ouyang Guifang, Duan Shiwei
Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China.
Department of Hematology, Ningbo First Hospital, Ningbo, Zhejiang 315010, P.R. China.
Mol Clin Oncol. 2016 Sep;5(3):193-207. doi: 10.3892/mco.2016.959. Epub 2016 Jul 12.
Mounting evidence supports a role for DNA methylation in the pathogenesis of leukemia; however, there no overview of these results in the Chinese population. The present study performed a comprehensive meta-analysis to establish candidate genes with an altered methylation status in Chinese leukemia patients. Eligible studies were identified through searching the National Center of Biotechnology Information PubMed and Wanfang databases. Studies were pooled and overall odds ratios with corresponding confidence intervals were calculated. A total of 4,325 leukemia patients and 2,010 controls from 94 studies on 53 genes were included in this meta-analysis, and 47 genes were found to be aberrantly methylated in leukemia patients. A further subgroup meta-analysis by leukemia subtype demonstrated that hypermethylation of 5 genes, namely cyclin-dependent kinase (), DNA-binding protein inhibitor-4, , glioma pathogenesis-related protein 1 and , contributed to the risk of various subtypes of leukemia. In addition, a strong association between and leukemia was identified in Chinese (P<0.00001) but not in European patients. The aberrantly methylated genes identified in the present meta-analysis may help elucidate the mechanisms underlying the development of leukemia in Chinese patients.
越来越多的证据支持DNA甲基化在白血病发病机制中发挥作用；然而，目前尚无针对中国人群这些研究结果的综述。本研究进行了一项全面的荟萃分析，以确定中国白血病患者中甲基化状态改变的候选基因。通过检索美国国立生物技术信息中心的PubMed数据库和万方数据库来确定符合条件的研究。对研究进行汇总，并计算总体比值比及相应的置信区间。本荟萃分析纳入了来自94项关于53个基因研究的总共4325例白血病患者和2010例对照，发现47个基因在白血病患者中存在异常甲基化。进一步按白血病亚型进行亚组荟萃分析表明，细胞周期蛋白依赖性激酶（）、DNA结合蛋白抑制因子4、、胶质瘤发病相关蛋白1和这5个基因的高甲基化增加了各类白血病亚型的发病风险。此外，在中国人群中发现与白血病存在强关联（P<0.00001），但在欧洲患者中未发现。本荟萃分析中确定的异常甲基化基因可能有助于阐明中国白血病患者发病的潜在机制。
