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

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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.

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Acknowledgment

The authors would like to thank to Dr. Adriana Stan, Genetic Lab, Bucharest, Romania, for her help with the sequencing experiments.

Authorship and conflict of interest disclosure

APT designed research, performed genetic analysis, analyzed data, and wrote the manuscript. AC designed research, collected the samples and patients data, analyzed data, and wrote the manuscript. LP, LU, and DD collected the samples and patients data. MSM and IVP performed genetic analysis. RAP designed research and analyzed data.

The authors reported no potential conflict of interest.

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Authors and Affiliations

  1. Department of Medical Genetics, “Iuliu Hatieganu” University of Medicine and Pharmacy, 6 Pasteur St, 400349, Cluj-Napoca, Romania

    Adrian P. Trifa, Mariela S. Militaru, Ioan V. Pop & Radu A. Popp

  2. Department of Hematology, “Ion Chiricuta” Cancer Institute, Cluj-Napoca, Romania

    Andrei Cucuianu, Ljubomir Petrov, Laura Urian & Delia Dima

Authors
  1. Adrian P. Trifa
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  2. Andrei Cucuianu
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  3. Ljubomir Petrov
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  4. Laura Urian
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  5. Mariela S. Militaru
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  6. Delia Dima
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  7. Ioan V. Pop
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  8. Radu A. Popp
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Correspondence to Adrian P. Trifa.

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Trifa, A.P., Cucuianu, A., Petrov, L. et al. The G allele of the JAK2 rs10974944 SNP, part of JAK2 46/1 haplotype, is strongly associated with JAK2 V617F-positive myeloproliferative neoplasms. Ann Hematol 89, 979–983 (2010). https://doi.org/10.1007/s00277-010-0960-y

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  • DOI: https://doi.org/10.1007/s00277-010-0960-y

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