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Titolo:
Allelic, genotypic and phenotypic distributions of S-mephenytoin 4 '-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world
Autore:
Xie, HG; Stein, CM; Kim, RB; Wilkinson, GR; Flockhart, DA; Wood, AJJ;
Indirizzi:
Vanderbilt Univ, Med Ctr, Div Clin Pharmacol, Sch Med,Dept Med, Nashville,TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 d,Dept Med, Nashville,TN 37232 USA Vanderbilt Univ, Med Ctr, Div Clin Pharmacol, Sch Med,Dept Pharmacol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Pharmacol, Nashville, TN 37232 USA Georgetown Univ, Med Ctr, Div Clin Pharmacol, Pharmacogenet Core Lab, Washington, DC 20007 USA Georgetown Univ Washington DC USA 20007 ore Lab, Washington, DC 20007 USA
Titolo Testata:
PHARMACOGENETICS
fascicolo: 5, volume: 9, anno: 1999,
pagine: 539 - 549
SICI:
0960-314X(199910)9:5<539:AGAPDO>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
POOR METABOLIZER PHENOTYPE; DRUG-METABOLISM; HYDROXYLATION PHENOTYPES; GENETIC POLYMORPHISMS; CHINESE POPULATIONS; INTERETHNIC DIFFERENCES; OMEPRAZOLE METABOLISM; PROGUANIL METABOLISM; DIAZEPAM METABOLISM; TURKISH POPULATION;
Keywords:
CYP2C19; S-mephenytoin 4 '-hydroxylation; pharmacogenetics; genetic polymorphism; phenotype; genotype; allele; SNP; Caucasians; meta-analysis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
77
Recensione:
Indirizzi per estratti:
Indirizzo: Wood, AJJ Vanderbilt Univ, Med Ctr, Div Clin Pharmacol, Sch Med,Dept Med, Room 550,MRB-1, Nashville, TN 37232 USA Vanderbilt Univ Room 550,MRB-1 Nashville TN USA 37232 37232 USA
Citazione:
H.G. Xie et al., "Allelic, genotypic and phenotypic distributions of S-mephenytoin 4 '-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world", PHARMACOGEN, 9(5), 1999, pp. 539-549

Abstract

Impaired S-mephenytoin 4'-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. The reported population prevalence of the CYP2C19 poor metabolizer phenotype in Caucasians of European descent has been described as ranging from 0.9% to 7.7%. To address the question of whether the difference in the frequency of poor metabolizers represents an ethnic genetic microheterogeneity in the structure and expression of the CYP2C19 gene in Caucasian individuals, we performed a pooled analysis of available studies. Combined data from the 22 homogeneous studies showed that the frequency of poor metabolizers in healthy unrelated Caucasians determined by phenotyping was 2.8% (110 of 3990; 95% confidence interval 2.3-3.3), Data obtained from eight homogeneous studies that determined the frequency of poor metabolizers by genotyping showed that the genotypic frequency of poor metabolizers was 2.1% (28 of 1356; 95% confidence interval 1.3-2.8), consistent with the poor metabolizer frequency determined by phenotyping. In the extensive metabolizers, 26% (471 of 1786; 95% confidence interval 24.4-28.4) were heterozygotes. The observed frequencies of the three Mendelian genotypes were 73% for wt/wt, 26% for wt/m, and 2.1% for m/m. Based on the overall phenotypic poor metabolizer frequency of 2.8%, the expected genotypic frequencies were 69% for wt/wt, 28% for wt/m and 2.8% for mim, which are in good agreement to the observed values. However, in the 84 Caucasian phenotyped and genotyped poor metabolizers, approximately 10% of the putative poor metabolizer alleles(17 of 168) were unknown. This study provides a systematic overview of the population distribution of the CYP2C19 poor metabolizer phenotype and CYP2C19 alleles and genotypes in healthy Caucasians living in different geographical areas, and shows a similar polymorphic pattern in the structure and expression of the CYP2C19 gene in the worldwide Caucasian populations. Pharmacogenetics 9:539-549 (C) 1999 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 03:27:21