RGD Reference Report - HFE C282Y mutation as a genetic modifier influencing disease susceptibility for chronic myeloproliferative disease. - Rat Genome Database

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HFE C282Y mutation as a genetic modifier influencing disease susceptibility for chronic myeloproliferative disease.

Authors: Andrikovics, H  Meggyesi, N  Szilvasi, A  Tamaska, J  Halm, G  Lueff, S  Nahajevszky, S  Egyed, M  Varkonyi, J  Mikala, G  Sipos, A  Kalasz, L  Masszi, T  Tordai, A 
Citation: Andrikovics H, etal., Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):929-34. doi: 10.1158/1055-9965.EPI-08-0359. Epub 2009 Mar 3.
RGD ID: 10755491
Pubmed: PMID:19258483   (View Abstract at PubMed)
DOI: DOI:10.1158/1055-9965.EPI-08-0359   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myelofibrosis no_associationIAGP 10755491DNA:missense mutation:exon:p.H63D (c.408C>G) (rs1799945) (human)RGD 
myelofibrosis susceptibilityIAGP 10755491DNA:missense mutation:exon:p.C282Y (c.1066G>A) (rs1800562) (human)RGD 
myelofibrosis no_associationISOHFE (Homo sapiens)10755491; 10755491DNA:missense mutation:exon:p.H63D (c.408C>G) (rs1799945) (human)RGD 
myelofibrosis susceptibilityISOHFE (Homo sapiens)10755491; 10755491DNA:missense mutation:exon:p.C282Y (c.1066G>A) (rs1800562) (human)RGD 
polycythemia vera susceptibilityIAGP 10755491DNA:missense mutation:exon:p.C282Y (c.1066G>A) (rs1800562) (human)RGD 
polycythemia vera no_associationIAGP 10755491DNA:missense mutation:exon:p.H63D (c.408C>G) (rs1799945) (human)RGD 
polycythemia vera no_associationISOHFE (Homo sapiens)10755491; 10755491DNA:missense mutation:exon:p.H63D (c.408C>G) (rs1799945) (human)RGD 
polycythemia vera susceptibilityISOHFE (Homo sapiens)10755491; 10755491DNA:missense mutation:exon:p.C282Y (c.1066G>A) (rs1800562) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Bone marrow hypercellularity susceptibilityIAGP 10755491DNA:missense mutation:exon:p.C282Y (c.1066G>A) (rs1800562)RGD 
Bone marrow hypercellularity no_associationIAGP 10755491DNA:missense mutation:exon:p.H63D (c.408C>G) (rs1799945)RGD 
Myelofibrosis susceptibilityIAGP 10755491DNA:missense mutation:exon:p.C282Y (c.1066G>A) (rs1800562)RGD 
Myelofibrosis no_associationIAGP 10755491DNA:missense mutation:exon:p.H63D (c.408C>G) (rs1799945)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Hfe  (homeostatic iron regulator)

Genes (Mus musculus)
Hfe  (homeostatic iron regulator)

Genes (Homo sapiens)
HFE  (homeostatic iron regulator)


Additional Information