title: The JAK2 46/1 haplotype in Budd-Chiari syndrome and portal vein thrombosis.
abstract: 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.
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jasper H
authors.initials: JH
authors.lastname: Smalberg
authors.forename: Edith
authors.initials: E
authors.lastname: Koehler
authors.forename: Sarwa
authors.initials: S
authors.lastname: Darwish Murad
authors.forename: Aurelie
authors.initials: A
authors.lastname: Plessier
authors.forename: Susana
authors.initials: S
authors.lastname: Seijo
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.forename: Massimo
authors.initials: M
authors.lastname: Primignani
authors.forename: Moniek P M
authors.initials: MP
authors.lastname: de Maat
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Garcia-Pagan
authors.forename: Dominique C
authors.initials: DC
authors.lastname: Valla
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
mesh_terms: D000328:Adult; D006502:Budd-Chiari Syndrome / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006239:Haplotypes; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D013152:Splanchnic Circulation; D020246:Venous Thrombosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; C507924:JAK2 protein, human; D053614:Janus Kinase 2