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JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms
- Source :
- Nature Genetics. 41:446-449
- Publication Year :
- 2009
- Publisher :
- Springer Science and Business Media LLC, 2009.
-
Abstract
- Chronic myeloproliferative neoplasms (MPNs) are a group of related conditions characterized by the overproduction of cells from one or more myeloid lineages. More than 95% of cases of polycythemia vera, and roughly half of essential thrombocythemia and primary myelofibrosis acquire a unique somatic 1849G>T JAK2 mutation (encoding V617F) that is believed to be a critical driver of excess proliferation. We report here that JAK2(V617F)-associated disease is strongly associated with a specific constitutional JAK2 haplotype, designated 46/1, in all three disease entities compared to healthy controls (polycythemia vera, n = 192, P = 2.9 x 10(-16); essential thrombocythemia, n = 78, P = 8.2 x 10(-9) and myelofibrosis, n = 41, P = 8.0 x 10(-5)). Furthermore, JAK2(V617F) specifically arises on the 46/1 allele in most cases. The 46/1 JAK2 haplotype thus predisposes to the development of JAK2(V617F)-associated MPNs (OR = 3.7; 95% CI = 3.1-4.3) and provides a model whereby a constitutional genetic factor is associated with an increased risk of acquiring a specific somatic mutation.
- Subjects :
- Male
Heterozygote
Myeloid
Genotype
Polymorphism, Single Nucleotide
Article
Polycythemia vera
Germline mutation
hemic and lymphatic diseases
Genetics
medicine
Humans
Genetic Predisposition to Disease
Allele
Myelofibrosis
Polycythemia Vera
Janus kinase 2
Models, Genetic
biology
Essential thrombocythemia
Homozygote
Haplotype
Janus Kinase 2
medicine.disease
Thrombocytopenia
Pedigree
medicine.anatomical_structure
Amino Acid Substitution
Haplotypes
Hematologic Neoplasms
Immunology
biology.protein
Female
Subjects
Details
- ISSN :
- 15461718 and 10614036
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....3d7544b9fc78cf51c415787c7eff027b