Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: Polymorphism in RFLP and DNA sequence of CYP2D6

Su‐Lan ‐L Wang, Jin‐Ding ‐D Huang, Ming-Derg Lai, Biing‐Hui ‐H Liu, Ming‐Liang ‐L Lai

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178 Citations (Scopus)

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 CYP2D6 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 (G 1934 ) to adenine (A) mutation, commonly found in white poor metabolizers. Approximately 70% of alleles showed thymine at 188 base pairs (T 188 ), and 76% showed cytosine at 4268 base pairs (C 4268 ) instead of C 188 and G 4268 , as is found in most white subjects. Subjects with T 188 or C 42 68 showed a significant higher log(MR) than subjects with homozygous C 188 and G 4268 . The C/T 188 , G/A 1934 , G/C 4268 , and RFLP polymorphisms may explain the interracial variations between Chinese and white subjects, as well as the genetic variations among Chinese subjects. Clinical Pharmacology and Therapeutics (1993) 53, 410–418; doi:

Original languageEnglish
Pages (from-to)410-418
Number of pages9
JournalClinical Pharmacology & Therapeutics
Volume53
Issue number4
DOIs
Publication statusPublished - 1993 Jan 1

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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