Germline variations at JAK2 , TERT , HBS1L - MYB and MECOM and the risk of myeloproliferative neoplasms in Taiwanese population

// Yi-Hao Chiang 1, 2, * , Yu-Cheng Chang 1, 2, 3 * , Huan-Chau Lin 1, 2 , Ling Huang 2 , Chun-Chia Cheng 1, 2 , Wei-Ting Wang 1 , Hung-I Cheng 4 , Nai-Wen Su 1, 2, 3 , Caleb Gon-Shen Chen 1, 2, 3, 5 , Johnson Lin 1, 2 , Yi-Fang Chang 1, 2, 3 , Ming-Chih Chang 1, 2, 3 , Ruey-Kuen Hsieh 1, 2 , Wen-Chien Chou 6, 7 , Ken-Hong Lim 1, 2, 3, 8 and Yuan-Yeh Kuo 8 1 Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan 2 Laboratory of Good Clinical Research Center, Department of Medical Research, MacKay Memorial Hospital, New Taipei City, Taiwan 3 Department of Medicine, MacKay Medical College, New Taipei City, Taiwan 4 Division of Hematology and Oncology, Department of Internal Medicine, MacKay Memorial Hospital, Hsinchu, Taiwan 5 Institute of Molecular and Cellular Biology, National Tsing-Hua University, Hsinchu, Taiwan 6 Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan 7 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan 8 Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan * Co-first authors, these authors contributed equally to this work Correspondence to: Ken-Hong Lim, email: khlim@mmh.org.tw Yuan-Yeh Kuo, email: yykuo@ntu.edu.tw Keywords: JAK2, TERT, myeloproliferative neoplasms, single nucleotide polymorphism Received: September 16, 2016      Accepted: June 09, 2017      Published: July 12, 2017 ABSTRACT Germline variations at JAK2 , TERT , HBS1L - MYB and MECOM 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 ( JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L - MYB rs9376092 and MECOM 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 JAK2 46/1 haplotype, JAK2 rs12339666 and TERT rs2736100 were significantly associated with Taiwanese MPNs ( P = 3.6x10 -19 , 1.9x10 -19 and 3.1x10 -6 , respectively), and JAK2 V617F -positive MPNs (n=121) ( P = 5.6x10 -21 , 4.4x10 -21 and 8.6x10 -7 , respectively). In JAK2 V617F -negative cases (n=55), only the JAK2 46/1 haplotype and JAK2 rs12339666 remained statistically significant ( P = 0.009 and 0.007, respectively). When stratified by disease subtypes, the JAK2 46/1 haplotype and JAK2 rs12339666 were significantly associated with all three MPN subtypes, but TERT rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with CALR mutations in our cohort. Furthermore, the risk alleles of MECOM rs2201862 and HBS1L - MYB rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at JAK2 (both the 46/1 haplotype and rs12339666) and TERT rs2736100 were associated with MPNs in Taiwanese population.