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Titolo:
Study of the association between cytochromes P450 2D6 and 2E1 genotypes and the risk of drug and chemical induced idiosyncratic aplastic anaemia
Autore:
Marsh, JCW; Chowdry, J; Parry-Jones, N; Ellis, SW; Muir, KR; Gordon-Smith, EC; Tucker, GT;
Indirizzi:
St George Hosp, Sch Med, Dept Haematol, London SW17 0RE, England St GeorgeHosp London England SW17 0RE aematol, London SW17 0RE, England Univndottingham, Sch Med, Dept Epidemiol & Publ Hlth Med, Nottingham, Engla Univ Nottingham Nottingham England l & Publ Hlth Med, Nottingham, Engla UnivYorkshire,, Royal Hallamshire Hosp, Dept Med & Pharmacol, Sheffield, SUniv Sheffield Sheffield S Yorkshire England d & Pharmacol, Sheffield, S
Titolo Testata:
BRITISH JOURNAL OF HAEMATOLOGY
fascicolo: 2, volume: 104, anno: 1999,
pagine: 266 - 270
SICI:
0007-1048(199902)104:2<266:SOTABC>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CLOZAPINE-INDUCED AGRANULOCYTOSIS; POOR METABOLIZER PHENOTYPE; POLYMORPHIC HYDROXYLATION; MARROW TRANSPLANTATION; ANEMIA; DEBRISOQUINE; CYP2D6; GENE; ALLELE; IDENTIFICATION;
Keywords:
idiosyncratic aplastic anaemia; drug metabolism; CYP2D6 gene; GYP2E1 gene;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Marsh, JCW Standorge Hosp, Sch Med, Dept Haematol, Cranmer Terr, London SW17 0RE, Engl St George Hosp Cranmer Terr London England SW17 0RE 0RE, Engl
Citazione:
J.C.W. Marsh et al., "Study of the association between cytochromes P450 2D6 and 2E1 genotypes and the risk of drug and chemical induced idiosyncratic aplastic anaemia", BR J HAEM, 104(2), 1999, pp. 266-270

Abstract

A genetic susceptibility to drug or chemical toxicity may provide a basis for an increased risk of idiosyncratic aplastic anaemia (AA). The cytochrome P450 enzymes are responsible for the metabolism of many drugs, some of which have been linked to AA. Mutations in the cytochrome P450 CYP2D6 gene result in absent or impaired enzyme activity in about 7% of Caucasians, whereas a specific mutation in the 5'-regulatory region of the CYP2E1 gene causes overexpression of the gene. We evaluated the frequency of allelic variants of CYP2D6 and CYP2E1 using allele-specific PCR amplification and restriction enzyme analysis of blood mononuclear cell DNA among 54 Caucasian AA patients. CYP2D6 and CYP2E1 were chosen because of the link between AA and theantipsychotic drug remoxipride (CYP2D6 substrate) and benzene (CYP2E1 substrate), respectively Results were compared with 53 controls matched for age, sex and ethnicity The percentage of AA patients homozygous for the CYP2D6*3, CYP2D6*4 alleles (poor metabolizer phenotype) and the CYP2E1 mutant allele (overexpression) was 0%, 4% and 0%, respectively, and the percentage ofheterozygotes was 2%, 28% and 15%, respectively. For normal controls the corresponding results for homozygous mutants were 0%, 4% and 0% and for heterozygotes 4%, 25% and 6%, respectively. We concluded that there were no major differences in the frequencies of the genetic polymorphisms between thisseries of AA patients and controls, but due to the low number of cases with the poor metabolizer phenotype and those with a history of drug exposure,the power of the study was too low to disprove an interaction.

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Documento generato il 29/01/20 alle ore 19:09:11