The JAK2 46/1 haplotype is a risk factor for myeloproliferative neoplasms in Chinese patients
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ORIGINAL ARTICLE
The JAK2 46/1 haplotype is a risk factor for myeloproliferative neoplasms in Chinese patients Xinju Zhang • Tingting Hu • Zhiyuan Wu Zhihua Kang • Weiwei Liu • Ming Guan
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Received: 4 June 2012 / Revised: 23 August 2012 / Accepted: 27 August 2012 / Published online: 29 September 2012 Ó The Japanese Society of Hematology 2012
Abstract The presence of JAK2 V617F is associated with an inherited JAK2 46/1 haplotype, a risk factor for myeloproliferative neoplasms (MPN) in Caucasian populations. Whether the JAK2 46/1 haplotype is also a risk factor in the Chinese population is unknown. We assessed for the JAK2 46/1 haplotype and JAK2 V617F mutation in 225 MPN patients and 226 controls using a tagged SNP rs12340895. The allele frequencies of the JAK2 46/1 haplotype were distinct among different subtypes of MPN patients. The allele frequency was significantly higher in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) than that in controls, with PV patients having the highest allele frequency (0.58, P = 6.00E-15). The distribution of rs12340895 genotypes in the JAK2 V617F mutated MPN patients was significantly different from that in controls (P = 1.67E-15). The percentage of GG genotype in controls was 2.2 %, but 31.0 % in JAK2 V617F-positive MPN patients. All the PV, ET, and PMF patients with the GG genotype also exhibited the V617F mutation. Compared to that of controls, the difference in genotype distribution in PV patients was the most significant (P = 4.83E-21), followed by ET (P = 2.07E-05) and PMF (P = 1.99E-04). Our results suggest that the X. Zhang and T. Hu equally contributed to this study. X. Zhang M. Guan (&) Department of Central Laboratory, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Central Urumqi Road, Shanghai 200040, People’s Republic of China e-mail: [email protected] T. Hu Z. Wu Z. Kang W. Liu (&) M. Guan Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, 12 Central Urumqi Road, Shanghai 200040, People’s Republic of China e-mail: [email protected]
JAK2 46/1 haplotype is a risk factor for MPN in the Chinese population, and patients with GG genotype in rs12340895 locus are susceptible to JAK2 V617F mutation. Keywords neoplasms
JAK2 V617F SNP Myeloproliferative
Introduction Myeloproliferative neoplasm (MPN) arises from the precursors of the myeloid lineage and represents a group of diseases of the bone marrow, in which excessive cells are produced. Somatic acquisition of genetic aberrations may be one of the pathogenic mechanisms, and it is widely believed that inherited genetic factors play an important role in the development of MPNs [1, 2]; however, the underlying molecular mechanisms remain to be determined. Identification of the V617F mutation of the JAK2 gene (JAK2 V617F) is a breakthrough in the understanding of the molecular mechanisms of the majority of MPN diseases [3–6]. JAK2 is a non-receptor tyrosine kinase involved in a specific subset of cy
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