G allele of the JAK2 rs10974944 SNP, part of JAK2 46/1 haplotype, is strongly associated with JAK2 V617F-positive myeloproliferative neoplasms

• Published in: Annals of hematology Vol. 89; no. 10; pp. 979 - 983
• Main Authors: Trifa, Adrian P, Cucuianu, Andrei, Petrov, Ljubomir, Urian, Laura, Militaru, Mariela S, Dima, Delia, Pop, Ioan V, Popp, Radu A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01-10-2010; Springer-Verlag; Springer Nature B.V
• Subjects: Alleles; Genotype; Haplotypes; Hematologic Neoplasms - enzymology; Hematologic Neoplasms - genetics; Hematology; Humans; JAK2 46/1 haplotype; JAK2 rs10974944 SNP; JAK2 V617F; Janus Kinase 2 - genetics; Medicine; Medicine & Public Health; Middle Aged; Mutation; Myeloproliferative Disorders - enzymology; Myeloproliferative Disorders - genetics; Myeloproliferative neoplasms; Oncology; Original Article; Polymorphism, Single Nucleotide; rs10974944 SNP; 46/1 haplotype; V617F; Myeloproliferative neoplasms
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-010-0960-y

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.