Show simple item record

dc.contributor.authorPardanani, Animesh Dev
dc.contributor.authorFridley, Brooke L.
dc.contributor.authorLasho, Terra L.
dc.contributor.authorGilliland, D. Gary
dc.contributor.authorTefferi, Ayalew
dc.date2022-08-11T08:08:51.000
dc.date.accessioned2022-08-23T16:10:08Z
dc.date.available2022-08-23T16:10:08Z
dc.date.issued2007-11-17
dc.date.submitted2009-02-19
dc.identifier.citationBlood. 2008 Mar 1;111(5):2785-9. Epub 2007 Nov 15. <a href="http://dx.doi.org/10.1182/blood-2007-06-095703">Link to article on publisher's site</a>
dc.identifier.issn0006-4971 (Print)
dc.identifier.doi10.1182/blood-2007-06-095703
dc.identifier.pmid18006699
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32864
dc.description.abstractJAK2V617F is an acquired mutation associated with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We tested the hypothesis that the paradox of a single disease allele associated with 3 distinctive clinical phenotypes could be explained in part by host-modifying influences. We screened for genetic variation within 4 candidate genes involved in JAK-STAT signaling, including receptors for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony-stimulating factor (GCSFR), and JAK2. We genotyped 32 linkage disequilibrium tag single nucleotide polymorphism (SNP) loci in 179 white patients: 84 had PV, 58 had PMF, and 37 had ET. Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF. Three additional JAK2 SNPs (rs10758669, rs3808850, and rs10974947) and a single EPOR SNP (rs318699) were also significantly associated with PV but not with ET or PMF. Finally, intragene haplotypes in JAK2 were significantly associated with PV only. Thus, host genetic variation may contribute to phenotypic diversity among myeloproliferative disorders, including in the presence of a shared disease allele.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18006699&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1182/blood-2007-06-095703
dc.subjectAdolescent; Adult; Aged; Aged, 80 and over; Demography; Female; Genetic Predisposition to Disease; *Genetic Variation; Haplotypes; Humans; Janus Kinase 2; Linkage Disequilibrium; Male; Middle Aged; Myeloproliferative Disorders; Phenotype; Polycythemia Vera; Polymorphism, Single Nucleotide; Regression Analysis; Thrombocythemia, Essential
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleHost genetic variation contributes to phenotypic diversity in myeloproliferative disorders
dc.typeJournal Article
dc.source.journaltitleBlood
dc.source.volume111
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1418
dc.identifier.contextkey727706
html.description.abstract<p>JAK2V617F is an acquired mutation associated with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We tested the hypothesis that the paradox of a single disease allele associated with 3 distinctive clinical phenotypes could be explained in part by host-modifying influences. We screened for genetic variation within 4 candidate genes involved in JAK-STAT signaling, including receptors for erythropoietin (EPOR), thrombopoietin (MPL), and granulocyte colony-stimulating factor (GCSFR), and JAK2. We genotyped 32 linkage disequilibrium tag single nucleotide polymorphism (SNP) loci in 179 white patients: 84 had PV, 58 had PMF, and 37 had ET. Genotype-phenotype analysis showed 3 JAK2 SNPs (rs7046736, rs10815148, and rs12342421) to be significantly but reciprocally associated with PV (P < .001 for all; odds ratio = 0.16, 2.72, and 2.46, respectively) and ET (P < .001 for all; odds ratio = 3.05, 0.29, and 0.30, respectively) but not with PMF. Three additional JAK2 SNPs (rs10758669, rs3808850, and rs10974947) and a single EPOR SNP (rs318699) were also significantly associated with PV but not with ET or PMF. Finally, intragene haplotypes in JAK2 were significantly associated with PV only. Thus, host genetic variation may contribute to phenotypic diversity among myeloproliferative disorders, including in the presence of a shared disease allele.</p>
dc.identifier.submissionpathgsbs_sp/1418
dc.contributor.departmentDivision of Hematology
dc.source.pages2785-9


This item appears in the following Collection(s)

Show simple item record