The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis

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 singlenucleotide 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 (PV617F-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.