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

Adrian P. Trifa (1) , Andrei Cucuianu (2) , Ljubomir Petrov (2) , Laura Urian (2) , Mariela S. Militaru (1) , Delia Dima (2) , Ioan V. Pop (1) , Radu A. Popp (1)

1 Department of Medical Genetics
2 Department of Hematology

Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are myeloproliferative neoplasms, characterized in a majority of cases by a unique somatic point mutation, V617F. Recently, it was shown that V617F occurs more frequently on a specific haplotype, named 46/1. We genotyped 149 myeloproliferative neoplasms patients (69 had polycythemia vera, 65 had essential thrombocythemia, and 15 had primary myelofibrosis) with a known V617F mutational status and 150 controls for the 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 ( < 0.0001). After stratifying for the 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 ( = 0.001), but not in V617F negative patients compared to controls ( = 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% ( = 0.0006). Our results indicate that the G allele, part of the 46/1 haplotype, contributes significantly to the occurrence of V617F-positive myeloproliferative neoplasms. Moreover, 46/1 seems to be associated with mutant allele burden >50% in V617F-positive myeloproliferative neoplasms patients.

Mots clés: Myeloproliferative neoplasms; V617F; 46/1 haplotype; rs10974944 SNP

Adrian P. Trifa, Andrei Cucuianu, Ljubomir Petrov, Laura Urian, Mariela S. Militaru, et al.. The G allele of the rs10974944 SNP, part of 46/1 haplotype, is strongly associated with V617F-positive myeloproliferative neoplasms. Annals of Hematology, 2010, 89 (10), pp.979-983. ⟨10.1007/s00277-010-0960-y⟩. ⟨hal-00529917⟩