Source:http://linkedlifedata.com/resource/pubmed/id/15834437
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2005-6-6
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| pubmed:abstractText |
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.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
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| pubmed:issn |
0268-3369
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
35
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1155-64
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15834437-Adult,
pubmed-meshheading:15834437-Alleles,
pubmed-meshheading:15834437-Breast Neoplasms,
pubmed-meshheading:15834437-Carbamoyl-Phosphate Synthase (Ammonia),
pubmed-meshheading:15834437-Female,
pubmed-meshheading:15834437-Genetic Predisposition to Disease,
pubmed-meshheading:15834437-Genotype,
pubmed-meshheading:15834437-Hematologic Neoplasms,
pubmed-meshheading:15834437-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:15834437-Hemochromatosis,
pubmed-meshheading:15834437-Hepatic Veno-Occlusive Disease,
pubmed-meshheading:15834437-Humans,
pubmed-meshheading:15834437-Iron,
pubmed-meshheading:15834437-Male,
pubmed-meshheading:15834437-Middle Aged,
pubmed-meshheading:15834437-Mutation, Missense,
pubmed-meshheading:15834437-Polymorphism, Genetic,
pubmed-meshheading:15834437-Polymorphism, Single-Stranded Conformational,
pubmed-meshheading:15834437-Prospective Studies,
pubmed-meshheading:15834437-Risk Factors
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.
|
| pubmed:affiliation |
Division of General Internal Medicine and Public Health, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37212, USA. Asha.Kallianpur@vanderbilt.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|