RGD Reference Report - The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation. - Rat Genome Database

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The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Authors: Kallianpur, AR  Hall, LD  Yadav, M  Byrne, DW  Speroff, T  Dittus, RS  Haines, JL  Christman, BW  Summar, ML 
Citation: Kallianpur AR, etal., Bone Marrow Transplant. 2005 Jun;35(12):1155-64.
RGD ID: 8694354
Pubmed: PMID:15834437   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.bmt.1704943   (Journal Full-text)

Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR=3.7, 95% CI 1.2-12.1) and increased progressively with C282Y allelic dose (RR=1.7, 95% CI 0.4-6.8 in heterozygotes; RR=8.6, 95% CI 1.5-48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HFEHumanhepatic veno-occlusive disease susceptibilityIAGP DNA:missense mutation:cds:p.C282Y (human)RGD 
HfeRathepatic veno-occlusive disease susceptibilityISOHFE (Homo sapiens)DNA:missense mutation:cds:p.C282Y (human)RGD 
HfeMousehepatic veno-occlusive disease susceptibilityISOHFE (Homo sapiens)DNA:missense mutation:cds:p.C282Y (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HFEHumanHyperbilirubinemia susceptibilityIAGP DNA:missense mutation:cds:p.C282YRGD 
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