title: The G allele of the JAK2 rs10974944 SNP, part of JAK2 46/1 haplotype, is strongly associated with JAK2 V617F-positive myeloproliferative neoplasms.
abstract: Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are myeloproliferative neoplasms, characterized in a majority of cases by a unique somatic point mutation, JAK2 V617F. Recently, it was shown that JAK2 V617F occurs more frequently on a specific JAK2 haplotype, named JAK2 46/1. We genotyped 149 myeloproliferative neoplasms patients (69 had polycythemia vera, 65 had essential thrombocythemia, and 15 had primary myelofibrosis) with a known JAK2 V617F mutational status and 150 controls for the JAK2 rs10974944 (C/G) single nucleotide polymorphism, in which the G allele tags the 46/1 haplotype. We found that the rs10974944 GG/CG genotypes were significantly enriched in patients compared to controls (p < 0.0001). After stratifying for the JAK2 V617F mutational status and for the mutant allele burden, we demonstrated that GG/CG genotypes were significantly more frequent in V617F positive compared to V617F negative patients (p = 0.001), but not in V617F negative patients compared to controls (p = 0.29). Similarly, the GG/CG genotypes were significantly enriched in V617F positive patients with a mutant allele burden >50% compared to those with a mutant allele burden <50% (p = 0.0006). Our results indicate that the G allele, part of the JAK2 46/1 haplotype, contributes significantly to the occurrence of JAK2 V617F-positive myeloproliferative neoplasms. Moreover, JAK2 46/1 seems to be associated with mutant allele burden >50% in JAK2 V617F-positive myeloproliferative neoplasms patients.
authors.affiliation: Department of Medical Genetics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania. adi_trifa@yahoo.co.uk
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Trifa
authors.forename: Andrei
authors.initials: A
authors.lastname: Cucuianu
authors.forename: Ljubomir
authors.initials: L
authors.lastname: Petrov
authors.forename: Laura
authors.initials: L
authors.lastname: Urian
authors.forename: Mariela S
authors.initials: MS
authors.lastname: Militaru
authors.forename: Delia
authors.initials: D
authors.lastname: Dima
authors.forename: Ioan V
authors.initials: IV
authors.lastname: Pop
authors.forename: Radu A
authors.initials: RA
authors.lastname: Popp
mesh_terms: D000483:Alleles; D005838:Genotype; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000201:enzymology / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000201:enzymology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D053614:Janus Kinase 2