Chiang Yi-Hao, Chang Yu-Cheng, Lin Huan-Chau, Huang Ling, Cheng Chun-Chia, Wang Wei-Ting, Cheng Hung-I, Su Nai-Wen, Chen Caleb Gon-Shen, Lin Johnson, Chang Yi-Fang, Chang Ming-Chih, Hsieh Ruey-Kuen, Chou Wen-Chien, Lim Ken-Hong, Kuo Yuan-Yeh
Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
Laboratory of Good Clinical Research Center, Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan.
Oncotarget. 2017 Jul 12;8(44):76204-76213. doi: 10.18632/oncotarget.19211. eCollection 2017 Sep 29.
Germline variations at , , - and have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations ( 46/1 haplotype tagged by rs12343867, intron 8 rs12339666, rs2736100, - rs9376092 and rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study. The information of 17033 control subjects was obtained from Taiwan Biobank database. The 46/1 haplotype, rs12339666 and rs2736100 were significantly associated with Taiwanese MPNs ( = 3.6×10, 1.9×10 and 3.1×10, respectively), and -positive MPNs (n=121) ( = 5.6×10, 4.4×10 and 8.6×10, respectively). In -negative cases (n=55), only the 46/1 haplotype and rs12339666 remained statistically significant (= 0.009 and 0.007, respectively). When stratified by disease subtypes, the 46/1 haplotype and rs12339666 were significantly associated with all three MPN subtypes, but rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with mutations in our cohort. Furthermore, the risk alleles of rs2201862 and - rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at (both the 46/1 haplotype and rs12339666) and rs2736100 were associated with MPNs in Taiwanese population.
在欧洲人群中，已发现 、 、 - 和 处的种系变异与骨髓增殖性肿瘤（MPN）相关。这些种系变异在台湾人群中是否与MPN相关尚不清楚。在此，我们旨在评估5种种系变异（由rs12343867标记的46/1单倍型、内含子8的rs12339666、rs2736100、 - rs9376092和rs2201862）与台湾人群MPN风险的关联。本研究共纳入178例MPN患者（109例原发性血小板增多症、54例真性红细胞增多症和15例原发性骨髓纤维化）。17033名对照受试者的信息来自台湾生物银行数据库。46/1单倍型、rs12339666和rs2736100与台湾MPN显著相关（分别为 = 3.6×10、1.9×10和3.1×10），与 -阳性MPN（n = 121）显著相关（分别为 = 5.6×10、4.4×10和8.6×10）。在 -阴性病例（n = 55）中，只有46/1单倍型和rs12339666仍具有统计学意义（分别为 = 0.009和0.007）。按疾病亚型分层时，46/1单倍型和rs12339666与所有三种MPN亚型均显著相关，但rs2736100仅与原发性血小板增多症和真性红细胞增多症相关。在我们的队列中，未发现这5个单核苷酸多态性（SNP）与 突变有任何关联。此外，rs2201862和 - rs9376092的风险等位基因被证明与发生真性红细胞增多症的风险呈负相关。总之， 处的种系变异（46/1单倍型和rs12339666）以及rs2736100与台湾人群的MPN相关。
