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Titolo:
DEBRISOQUINE AND S-MEPHENYTOIN HYDROXYLATION PHENOTYPES AND GENOTYPESIN A KOREAN POPULATION
Autore:
ROH HK; DAHL ML; JOHANSSON I; INGELMANSUNDBERG M; CHA YN; BERTILSSON L;
Indirizzi:
HUDDINGE HOSP,KAROLINSKA INST,DEPT MED LAB SCI & TECHNOL,DIV CLIN PHARMACOL S-14186 HUDDINGE SWEDEN HUDDINGE HOSP,KAROLINSKA INST,DEPT MED LAB SCI & TECHNOL,DIV CLIN PHARMACOL S-14186 HUDDINGE SWEDEN INHA UNIV,COLL MED,DEPT PHARMACOL & TOXICOL INCHON SOUTH KOREA KAROLINSKA INST,DEPT MED BIOCHEM & BIOPHYS S-17177 STOCKHOLM SWEDEN
Titolo Testata:
Pharmacogenetics
fascicolo: 5, volume: 6, anno: 1996,
pagine: 441 - 447
SICI:
0960-314X(1996)6:5<441:DASHPA>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENETIC-POLYMORPHISM; INTERETHNIC DIFFERENCES; SWEDISH POPULATION; CHINESE POPULATION; GAS-CHROMATOGRAPHY; POOR METABOLIZERS; MUTANT ALLELES; CYP2D6 GENE; JAPANESE; OXIDATION;
Keywords:
DEBRISOQUINE; MEPHENYTOIN; CYP2D6; CYP2C19; KOREANS; POLYMORPHISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
H.K. Roh et al., "DEBRISOQUINE AND S-MEPHENYTOIN HYDROXYLATION PHENOTYPES AND GENOTYPESIN A KOREAN POPULATION", Pharmacogenetics, 6(5), 1996, pp. 441-447

Abstract

One hundred and fifty-two healthy Korean volunteers were phenotyped with debrisoquine and mephenytoin and genotyped with respect to CYP2D6. The debrisoquine metabolic ratio (MR) varied between 0.09 and 6.3, and all subjects were thus classified as extensive metabolizers of debrisoquine. Polymerase chain reaction (PCR)-based amplification of genomic DNA with primers specific for the C-188-->T mutation present in exon1 of the CYP2D610B allele was performed and revealed an allele frequency of 0.51 in this Korean population. Forty-three subjects (28%) were homozygous for CYP2D610B, 69 subjects (45%) were heterozygous for this allele, while in 40 subjects (26%) no exon 1 mutation could be found. All subjects except one homozygous for the wild type allele had MRs below 0.75 whereas the MR was higher than 0.99 in all subjects homozygous for the CYP2D610B allele. The MRs in the three genotype groups were significantly different (p <0.0001; Kruskal-Wallis test). Eco RI RFLP analysis of DNA from six subjects with debrisoquine MRs less thanor equal to 0.11 revealed that only one (MR 0.09) carried a duplicated CYP2D62-gene (CYP2D6*2X2) as indicated by the Eco RI 12.1 kb haplotype. It is concluded that, as shown earlier for Chinese and Japanese populations, the CYP2D610B-allele containing the C-188-->T mutation isthe major cause of diminished CYP2D6 activity in Koreans. In this Korean population, the MR of debrisoquine was shifted towards higher values (lower CYP2D6 activity) compared with Caucasian populations but theshift appeared to be less pronounced than earlier shown for Chinese. Twenty-four subjects (16%) were poor metabolizers of S-mephenytoin as indicated by the SIR mephenytoin ratio of about 1. Twenty-three of these were genotyped with respect to the defect CYP2C19-alleles CYP2C192and CYP2C193. Of the 46 poor metabolizer alleles, 32 (70%) were CYP2C192 and the remaining 14 (30%) were CYP2C19*3. Thus, the defect CYP2C192 and CYP2C19*3-alleles explained 100% of the 23 Korean poor metabolizers of S-mephenytoin.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/20 alle ore 20:42:35