Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6.
Clin Pharmacol Ther
; 53(4): 410-8, 1993 Apr.
Article
em En
| MEDLINE
| ID: mdl-8097442
ABSTRACT
Debrisoquin hydroxylation phenotype was determined in 124 Chinese persons living in Taiwan, and two poor metabolizers were identified with a urinary metabolic ratio (MR) greater than 12.6. The other subjects, extensive metabolizers, showed a normal frequency distribution of log(MR). Most subjects (50%) showed a 44/29 kb pattern in restriction fragment length polymorphism (RFLP) analysis with use of Xba I, and 30% and 15% of the subjects exhibited a homozygous 29/29 kb and 44/44 kb pattern, respectively. Among extensive metabolizers, subjects with the 44/44 kb pattern had a significant higher log(MR) than those with the 44/29 pattern, and the log(MR) of the subjects with the 44/29 kb pattern was significantly higher than that of the subjects with 29/29 kb pattern. All nine exons and intron 3 of C gamma P2D6 were amplified with polymerase chain reaction (PCR) and sequenced for four extensive metabolizers. Two major polymorphisms were found one at position 188 of exon 1 and the other at position 4268 in exon 9. With PCR and endonuclease digestion, polymorphisms at exon 1, intron 3, and exon 9 were investigated. Only two of 254 alleles showed a heterozygous guanine at 1934 base pairs (G1934) to adenine (A) mutation, commonly found in white poor metabolizers. Approximately 70% of alleles showed thymine at 188 base pairs (T188), and 76% showed cytosine at 4268 base pairs (C4268) instead of C188 and G4268, as is found in most white subjects. Subjects with T188 or C4268 showed a significant higher log(MR) than subjects with homozygous C188 and G4268. The C/T188, G/A1934, G/C4268, and RFLP polymorphisms may explain the interracial variations between Chinese and white subjects, as well as the genetic variations among Chinese subjects.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimorfismo de Fragmento de Restrição
/
DNA
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Sistema Enzimático do Citocromo P-450
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Debrisoquina
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Povo Asiático
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Oxigenases de Função Mista
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Clin Pharmacol Ther
Ano de publicação:
1993
Tipo de documento:
Article
País de afiliação:
Taiwan