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Titolo:
Phenotypes and genotypes for CYP2D6 and CYP2C19 in a black Tanzanian population
Autore:
Bathum, L; Skjelbo, E; Mutabingwa, TK; Madsen, H; Horder, M; Brosen, K;
Indirizzi:
Odense Univ Hosp, Dept Clin Biochem, DK-5000 Odense C, Denmark Odense UnivHosp Odense Denmark C lin Biochem, DK-5000 Odense C, Denmark Odense Univ, Dept Clin Pharmacol, DK-5000 Odense, Denmark Odense Univ Odense Denmark DK-5000 in Pharmacol, DK-5000 Odense, Denmark Amani Med Res Ctr, Amani, Tanzania Amani Med Res Ctr Amani TanzaniaAmani Med Res Ctr, Amani, Tanzania
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 3, volume: 48, anno: 1999,
pagine: 395 - 401
SICI:
0306-5251(199909)48:3<395:PAGFCA>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
MEPHENYTOIN HYDROXYLATION PHENOTYPE; S-MEPHENYTOIN; GENETIC-POLYMORPHISM; DEBRISOQUINE HYDROXYLATION; ULTRARAPID METABOLIZERS; SPARTEINE METABOLISM; SWEDISH POPULATION; DANISH POPULATION; ALLELES; OXIDATION;
Keywords:
black population; CYP2C19; CYP2D6; genotype;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Bathum, L Odense Univ Hosp, Dept Clin Biochem, DK-5000 Odense C, Denmark Odense Univ Hosp Odense Denmark C m, DK-5000 Odense C, Denmark
Citazione:
L. Bathum et al., "Phenotypes and genotypes for CYP2D6 and CYP2C19 in a black Tanzanian population", BR J CL PH, 48(3), 1999, pp. 395-401

Abstract

Aims CYP2D6 and CYP2C19 are polymorphically expressed enzymes that show marked interindividual and interethnic variation. The aim of this study was to determine the frequency of the defective alleles in CYP2D6 and CYP2C19 inAfricans and to test whether the genotype for CYP2C19 is better correlatedwith the proguanil/cylcoguanil ratio than the mephenytoin S/R ratio. Methods Two hundred and sixteen black Tanzanians were phenotyped for CYP2D6 with the use of sparteine, and for CYP2C19 with the use of mephenytoin and proguanil. Of these 196 subjects were also genotyped for CYP2D6 (including the CYP2D6(star)1, CYP2D6(star)3 and CYP2Db(star)4 alleles) and 195 were genotyped for CYP2C19 (including the CYP2C19(star)1, CYP2C19(star)2 and theCYP2C19(star)3 alleles). Furthermore 100 subjects were examined for the allele duplication in CYP2D6, leading to ultrarapid metabolism, with long PCR. Results The sparteine metabolic ratio (MR) was statistically significantlyhigher in the Tanzanian group of homozygous, extensive metabolizers compared to a historical control soup of white Danish extensive metabolizers. Only one poor metabolizer for CYP2D6 (MR = 124 and genotype CYP2D6(star)1/CYP2D6(star)4) was found. The gene frequencies were 0.96 for the CYP2D6(star)1 allele and 0.04 for the CYP2D6(star)4 allele No CYP2D6(star)3 alleles were found. Nine subjects had an allele duplication in CYP2D6 (9%). For CYP2C19 there were seven subjects (3.6%) who were phenotyped as poor metabolizers, but only three subjects (1.5%) had a genotype (CYP2C19(star)2/CYP2C19(star)2) indicative of poor metabolism. The gene frequencies were 0.90 for the CYP2C19(star)1 allele and 0.10 for the CYP2C19(star)2 allele. No CYP2C19(star)3 alleles were found. The mephenytoin S/R ratios were not bimodally distributed. Conclusions Both the genotyping and phenotyping results show that there isa substantial difference between an African black population and a Caucasian population in the capacity to metabolize drugs via CYP2D6 and CYP2C19.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 07:31:30