title: HFE C282Y mutation as a genetic modifier influencing disease susceptibility for chronic myeloproliferative disease.
abstract: Iron metabolism has been implicated in carcinogenesis and several studies assessed the potential role of genetic variants of proteins involved in iron metabolism (HFE C282Y, TFR S142G) in different malignancies. Few reports addressed this issue with relation to chronic myeloproliferative disorders (CMPD). The aims of our study were (a) to examine the potential associations of CMPD development with genetic modifiers of iron metabolism in a large cohort of CMPD patients; (b) to examine associations of genetic variants of proteins involved in iron metabolism; and acquired JAK2 V617F mutation with clinical characteristics of CMPD. HFE C282Y was genotyped in 328 CMPD patients and 996 blood donors as controls, HFE H63D, and TFR S142G were tested in CMPD patients and 171 first time blood donors. JAK2 V617F mutation was tested in CMPD patients and in 122 repeated blood donors. Decreased C282Y allele frequency (allele frequency+/-95% confidence interval) was found in the CMPD group (1.8%+/-1.0%) compared with controls (3.4%+/-0.8%; P=0.048). TFR S142G allele frequency was reduced among V617F-negative CMPD patients (34.8%+/-7.6%) compared with controls (47.8%+/-5.4%; P=0.02). The frequency of JAK2 V617F was 75.9% (249 of 328) in the CMPD group. At presentation, elevated hemoglobin levels were found in V617F-positive patients compared with V617F-negative counterparts (P<0.000). Vascular complications (26.6% versus 15.2%; P=0.039) as well as female gender (57.4% versus 41.8%; P=0.019) were more common in V617F-positive patients. We found that HFE C282Y might be associated with a protective role against CMPD. Because chronic iron deficiency or latent anemia may trigger disease susceptibility for CMPD, HFE C282Y positivity may be a genetic factor influencing this effect.
authors.affiliation: National Blood Transfusion Service, Department of Hematology and Stem Cell Transplantation, St. Istvan and St. Laszlo Hospital of Budapest, and 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. andrikovics@kkk.org.hu
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Andrikovics
authors.forename: Nora
authors.initials: N
authors.lastname: Meggyesi
authors.forename: Aniko
authors.initials: A
authors.lastname: Szilvasi
authors.forename: Julia
authors.initials: J
authors.lastname: Tamaska
authors.forename: Gabriella
authors.initials: G
authors.lastname: Halm
authors.forename: Sandor
authors.initials: S
authors.lastname: Lueff
authors.forename: Sarolta
authors.initials: S
authors.lastname: Nahajevszky
authors.forename: Miklos
authors.initials: M
authors.lastname: Egyed
authors.forename: Judit
authors.initials: J
authors.lastname: Varkonyi
authors.forename: Gabor
authors.initials: G
authors.lastname: Mikala
authors.forename: Andrea
authors.initials: A
authors.lastname: Sipos
authors.forename: Laszlo
authors.initials: L
authors.lastname: Kalasz
authors.forename: Tamas
authors.initials: T
authors.lastname: Masszi
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001782:Blood Donors; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000150:complications / Q000235:genetics; D053614:Janus Kinase 2 / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D053614:Janus Kinase 2