Regular ArticleCharacterization of the Human Dihydropyrimidine Dehydrogenase Gene
References (40)
- et al.
Elevated urine, blood and cerebrospinal fluid levels of uracil and thymine in a child with dihydropyrimidine dehydrogenase deficiency
Clin. Chem. Acta
(1984) - et al.
Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency
Trends Pharmacol. Sci.
(1995) - et al.
Assignment of the human dihydropyrimidine dehydrogenase gene (DPYDin situ
Genomics
(1994) - et al.
Heterozygosity for a point mutation in an invariant splice donor site of dihydropyrimidine dehydrogenase and severe 5-fluorouracil related toxicity
Eur. J. Cancer
(1997) Degradation of pyrimidines and pyrimidine analogs—Pathways and mutual influences
Pharmacol. Ther.
(1980)- et al.
cDNA cloning and chromosome mapping of human dihydropyrimidine dehydrogenase, an enzyme associated with 5-fluorouracil toxicity and congenital thymine uraciluria
J. Biol. Chem.
(1994) - et al.
A new case of dihydropyrimidine dehydrogenase deficiency. Dihydropyrimidine dehydrogenase deficiency—A further case
J. Inherit. Metab. Dis. Suppl.
(1985) - et al.
An efficient strategy for detection of known and new mutations of the CYP2D6 gene using single strand conformation polymorphism analysis
Pharmacogenetics
(1995) - et al.
Isolation of single-copy human genes from a library of yeast artificial chromosome clones
Science
(1989) Deaths bring clinical trials under scrutiny in Japan
Nature
(1994)
Dihydropyrimidine dehydrogenase activity and fluorouracil chemotherapy
J. Clin. Oncol.
Lack of correlation between phenotype and genotype for the polymorphically expressed dihydropyrimidine dehydrogenase in a family of Pakistani origin
Pharmacogenetics
Dihydropyridine dehydrogenase activity in cancer patients
Eur. J. Cancer
Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion
Cancer Res.
Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome
Cancer
Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile
Cancer Res.
Partial epilepsy in a girl with a symptom-free sister: First two Finnish patients with dihydropyrimidine dehydrogenase deficiency
J. Inherit. Metab. Dis.
Structural organization of the human dihydropyrimidine dehydrogenase gene
Cancer Res.
Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: Population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy
Cancer Res.
Cited by (157)
Current diagnostic and clinical issues of screening for dihydropyrimidine dehydrogenase deficiency
2023, European Journal of CancerCitation Excerpt :Although other genes may play a role in FP toxicity (e.g. TYMS and MTHFR), and that complete DPD deficiency does not explain all FP toxicity-related deaths [1], DPYD non-functional variants are the main identified contributors of 5FU-related severe toxicities [30,31]. The DPYD gene encoding DPD, spans ∼900 kb on chromosome 1 and contains 23 exons [32]. DPYD is highly polymorphic, with more than 200 variants described in coding regions, but their effects on DPD enzyme activity are unknown for the majority of them [33–35].
Genetic polymorphisms on the effectiveness or safety of breast cancer treatment: Clinical relevance and future perspectives
2021, Mutation Research - Reviews in Mutation ResearchPurine and Pyrimidine Metabolism
2020, Emery and Rimoin’s Principles and Practice of Medical Genetics and Genomics: Metabolic DisordersPharmacogenomics in Cancer Therapeutics
2018, Pharmacogenomics: Challenges and Opportunities in Therapeutic ImplementationPrevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase deficiency screening: Assessment of a multiparametric approach
2017, Seminars in OncologyCitation Excerpt :Remarkably, DPD enzyme activity is subject to a wide variability, resulting in a possible range of enzymatic deficiencies that span from partial to complete loss of enzyme activity, with approximately 3%–5% of the entire population demonstrating partial deficiency and 0.2%–0.3% demonstrating complete deficiency (Fig. 2) [6,7]. DPD deficiency is partly linked to a genetic polymorphism since about 50% of patients who experienced early highly toxic and sometimes lethal effects were genotypically heterozygous or homozygous for known mutant alleles of the DPYD gene (Table 2) [8–11]. More than 30 variant DPD alleles have been published, and about half of them were considered to have potentially deleterious impact on DPD enzyme activity [12,13].
- 1
Contributed equally to this work.
- 2
Present address: Center for Drug Evaluation and Research, Food and Drug Administration, Parklawn Building, Rockville, MD 20857.
- 3
Present address: Laboratorio de Bioquimica y Biologia Molecular, Facultad de Ciencias, Universidad de Extremadura, 06080-Badajoz, Spain.
- 4
To whom correspondence should be addressed at Laboratory of Metabolism, National Cancer Institute, Building 37, Room 3E-24, Bethesda, MD, 20892. Telephone: (301) 496-9067. Fax: (301) 496-8419. E-mail:[email protected].