Source:http://linkedlifedata.com/resource/pubmed/id/14555507
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2003-10-13
|
| pubmed:abstractText |
Dihydropyrimidinase (DHP) is the second enzyme in the catabolism of 5-fluorouracil (5FU), and it has been suggested that patients with a deficiency of this enzyme are at risk from developing severe 5FU-associated toxicity. In this study, we demonstrated for the first time that in one patient the severe toxicity, after a treatment with 5FU, was attributable to a partial deficiency of DHP. Analysis of the DHP gene showed that the patient was heterozygous for the missense mutation 833G>A (G278D) in exon 5. Heterologous expression of the mutant enzyme in Escherichia coli showed that the G278D mutation leads to a mutant DHP enzyme without residual activity. An analysis for the presence of this mutation in 96 unrelated Dutch Caucasians indicates that the allele frequency in the normal population is <0.5%. Our results show that a partial DHP deficiency is a novel pharmacogenetic disorder associated with severe 5FU toxicity.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1078-0432
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
9
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4363-7
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:14555507-Amidohydrolases,
pubmed-meshheading:14555507-Amino Acid Sequence,
pubmed-meshheading:14555507-Antimetabolites, Antineoplastic,
pubmed-meshheading:14555507-Blotting, Western,
pubmed-meshheading:14555507-Breast Neoplasms,
pubmed-meshheading:14555507-Carcinoma, Ductal,
pubmed-meshheading:14555507-Chromatography, High Pressure Liquid,
pubmed-meshheading:14555507-DNA Mutational Analysis,
pubmed-meshheading:14555507-Escherichia coli,
pubmed-meshheading:14555507-Female,
pubmed-meshheading:14555507-Fluorouracil,
pubmed-meshheading:14555507-Humans,
pubmed-meshheading:14555507-Middle Aged,
pubmed-meshheading:14555507-Molecular Sequence Data,
pubmed-meshheading:14555507-Mutagenesis, Site-Directed,
pubmed-meshheading:14555507-Mutation, Missense,
pubmed-meshheading:14555507-Pharmacogenetics,
pubmed-meshheading:14555507-Polymerase Chain Reaction,
pubmed-meshheading:14555507-Purine-Pyrimidine Metabolism, Inborn Errors,
pubmed-meshheading:14555507-Transfection
|
| pubmed:year |
2003
|
| pubmed:articleTitle |
Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity.
|
| pubmed:affiliation |
Academic Medical Center, University of Amsterdam, Emma Children's Hospital, and Department of Clinical Chemistry, 1100 DE Amsterdam, The Netherlands. a.b.vankuilenburg@acm.uva.nl
|
| pubmed:publicationType |
Journal Article,
Case Reports
|