Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A MISSENSE MUTATION IN EXON-6 OF THE CYP2D6 GENE LEADING TO A HISTIDINE-324 TO PROLINE EXCHANGE IS ASSOCIATED WITH THE POOR METABOLIZER PHENOTYPE OF SPARTEINE
Autore:
EVERT B; GRIESE EU; EICHELBAUM M;
Indirizzi:
DR MARGARETE FISCHER BOSCH INST CLIN PHARMACOL,AUERBACHSTR 112 D-70376 STUTTGART GERMANY DR MARGARETE FISCHER BOSCH INST CLIN PHARMACOL D-70376 STUTTGART GERMANY
Titolo Testata:
Naunyn-Schmiedeberg's archives of pharmacology
fascicolo: 4, volume: 350, anno: 1994,
pagine: 434 - 439
SICI:
0028-1298(1994)350:4<434:AMMIEO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEBRISOQUINE METABOLISM; POLYMORPHISM; OXIDATION; HYDROXYLATION; POPULATION; DEFECT; IDENTIFICATION; DEFICIENT; SEQUENCE; ALLELES;
Keywords:
POOR METABOLIZER; SPARTEINE; CYP2D6 GENE; MISSENSE MUTATION IN EXON 6;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
B. Evert et al., "A MISSENSE MUTATION IN EXON-6 OF THE CYP2D6 GENE LEADING TO A HISTIDINE-324 TO PROLINE EXCHANGE IS ASSOCIATED WITH THE POOR METABOLIZER PHENOTYPE OF SPARTEINE", Naunyn-Schmiedeberg's archives of pharmacology, 350(4), 1994, pp. 434-439

Abstract

The sparteine/debrisoquine polymorphism is a clinically important genetic deficiency of cytochrome P4502D6-catalyzed oxidative drug metabolism. 5 - 10% of Caucasians designated as poor metabolizers have a severely impaired capacity to metabolize more than 30 therapeutically useddrugs. Genotyping of a random Caucasian population for the known cytochrome P4502D6 mutations A, B and D which are associated with the poormetabolizer phenotype has revealed a substantial number of misclassified poor metabolizers indicating the existence of one or more unknown mutations which cannot be identified with the currently available genotyping assays. Therefore we have cloned and sequenced one nonfunctional cytochrome P4502D6 allele of a misclassified poor metabolizer and could identify a single missense mutation designated E mutation at position 3023((A-C)) in exon 6. Direct sequencing analysis, FokI restriction analysis and a newly developed allele-specific polymerase chain reaction assay were applied to analyze for this mutation in a population study. Three out of 97 randomly selected Caucasians were carriers of this mutation and thus the E allele has a frequency of 1.5% (confidence interval(95%) = 0.33 - 4.54%). Since only 2 out of 4 misclassified poor metabolizers carried the E mutation, additional unknown mutant alleles must exist. Computer modelling suggests that the E mutation, which results in a histidine to proline exchange in position 324 of the protein, may cause an alteration of the 3D structure of CYP2D6 in close vicinity to the active site thereby leading to total loss of enzyme function.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 09:33:06