GSBS Student Publications

Title

Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders

UMMS Affiliation

Division of Hematology

Date

11-17-2007

Document Type

Article

Medical Subject Headings

Adolescent; 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

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Blood. 2008 Mar 1;111(5):2785-9. Epub 2007 Nov 15. Link to article on publisher's site

DOI of Published Version

10.1182/blood-2007-06-095703

Related Resources

Link to Article in PubMed

Journal Title

Blood

PubMed ID

18006699