Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Blood. 2011 Apr 14;117(15):3968-73. doi: 10.1182/blood-2010-11-319087. Epub 2011 Mar 1.
The germline JAK2 46/1 haplotype has been associated with the development of JAK2(V617F)-positive as well as JAK2(V617F)-negative myeloproliferative neoplasms (MPNs). In this study we examined the role of the 46/1 haplotype in the etiology and clinical presentation of patients with splanchnic vein thrombosis (SVT), in which MPNs are the most prominent underlying etiological factor. The single-nucleotide polymorphism rs12343867, which tags 46/1, was genotyped in 199 SVT patients. The 46/1 haplotype was overrepresented in JAK2(V617F)-positive SVT patients compared with controls (P < .01). Prevalence of the 46/1 haplotype in JAK2(V617F)-negative SVT patients did not differ from prevalence in the controls. However, JAK2(V617F)-negative SVT patients with a proven MPN also exhibited an increased frequency of the 46/1 haplotype (P = .06). Interestingly, 46/1 was associated with increased erythropoiesis in JAK2(V617F)-negative SVT patients. We conclude that the 46/1 haplotype is associated with the development of JAK2(V617F)-positive SVT. In addition, our findings in JAK2(V617F)-negative SVT patients indicate an important role for the 46/1 haplotype in the etiology and diagnosis of SVT-related MPNs, independent of JAK2(V617F), that requires further exploration.
胚系 JAK2 46/1 单倍型与 JAK2(V617F)-阳性以及 JAK2(V617F)-阴性骨髓增殖性肿瘤（MPN）的发展相关。在这项研究中，我们研究了 46/1 单倍型在脾静脉血栓形成（SVT）患者的病因学和临床表现中的作用，在这些患者中，MPN 是最突出的潜在病因。单核苷酸多态性 rs12343867 标记 46/1，在 199 例 SVT 患者中进行了基因分型。与对照组相比，JAK2(V617F)-阳性 SVT 患者中 46/1 单倍型过度表达（P <.01）。JAK2(V617F)-阴性 SVT 患者中 46/1 单倍型的患病率与对照组无差异。然而，具有明确 MPN 的 JAK2(V617F)-阴性 SVT 患者也表现出 46/1 单倍型的频率增加（P =.06）。有趣的是，46/1 与 JAK2(V617F)-阴性 SVT 患者的红细胞生成增加相关。我们的结论是，46/1 单倍型与 JAK2(V617F)-阳性 SVT 的发展相关。此外，我们在 JAK2(V617F)-阴性 SVT 患者中的发现表明，46/1 单倍型在 JAK2(V617F)阴性、与 SVT 相关的 MPN 的病因学和诊断中具有重要作用，独立于 JAK2(V617F)，这需要进一步探索。
