Analysis of the CΥP2D6 gene in relation to dextromethorphan O- demethylation capacity in a Japanese population

Tomonori Tateishi, Michihiro Chida, Noritaka Ariyoshi, Yoshihiro Mizorogi, Tetsuya Kamataki, Shinichi Kobayashi

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Abstract

Objective: To analyze the CΥP2D6 allele frequencies in a Japanese population and to evaluate the effects of CΥP2D6 variants on in vivo CΥP2D6 activity as measured by the dextromethorphan metabolic ratio (MR). Method: Ninety-eight unrelated, healthy Japanese men were phenotyped with dextromethorphan and genotyped by the polymerase chain reaction amplification method for 7 CΥP2D6 alleles. Results: The CΥP2D6*1, CΥP2D6*10, CΥP2D6*2, CΥP2D6*5, CΥP2D6*4, and CΥP2D6*21 allele frequencies in our Japanese subjects were 0.423, 0.408, 0.092, 0.061, 0.020, and 0.010, respectively. Thirty-three subjects (33.7%) were heterozygous for *10/*1, and 18 (18.4%) and 17 (17.3%) subjects were homozygous for *1 and *10, respectively. Subjects who were homozygous for *10 showed the highest dextromethorphan MR among these 3 genotypes. Eighteen subjects (18.3%) were heterozygous for *2, but their dextromethorphan MR values were not greater than the MR values of subjects who were homozygous for *1. One subject was a poor metabolizer phenotypically, and he was homozygous for *5. Conclusions: The CΥP2D6 allele frequencies in our Japanese subjects differed from those determined in previous studies of white subjects or mainland Chinese subjects. Individuals homozygous for *10 who have relatively low in vivo CΥP2D6 activity represent almost 20% of the Japanese population. In addition, we did not identify any subjects with amplified *2 among our 98 Japanese men.

Original languageEnglish
Pages (from-to)570-575
Number of pages6
JournalClinical Pharmacology and Therapeutics
Volume65
Issue number5
DOIs
Publication statusPublished - 1999
Externally publishedYes

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Dextromethorphan
Gene Frequency
Population
Genes
Alleles
Genotype
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Pharmacology

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Analysis of the CΥP2D6 gene in relation to dextromethorphan O- demethylation capacity in a Japanese population. / Tateishi, Tomonori; Chida, Michihiro; Ariyoshi, Noritaka; Mizorogi, Yoshihiro; Kamataki, Tetsuya; Kobayashi, Shinichi.

In: Clinical Pharmacology and Therapeutics, Vol. 65, No. 5, 1999, p. 570-575.

Research output: Contribution to journalArticle

Tateishi, Tomonori ; Chida, Michihiro ; Ariyoshi, Noritaka ; Mizorogi, Yoshihiro ; Kamataki, Tetsuya ; Kobayashi, Shinichi. / Analysis of the CΥP2D6 gene in relation to dextromethorphan O- demethylation capacity in a Japanese population. In: Clinical Pharmacology and Therapeutics. 1999 ; Vol. 65, No. 5. pp. 570-575.
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title = "Analysis of the CΥP2D6 gene in relation to dextromethorphan O- demethylation capacity in a Japanese population",
abstract = "Objective: To analyze the CΥP2D6 allele frequencies in a Japanese population and to evaluate the effects of CΥP2D6 variants on in vivo CΥP2D6 activity as measured by the dextromethorphan metabolic ratio (MR). Method: Ninety-eight unrelated, healthy Japanese men were phenotyped with dextromethorphan and genotyped by the polymerase chain reaction amplification method for 7 CΥP2D6 alleles. Results: The CΥP2D6*1, CΥP2D6*10, CΥP2D6*2, CΥP2D6*5, CΥP2D6*4, and CΥP2D6*21 allele frequencies in our Japanese subjects were 0.423, 0.408, 0.092, 0.061, 0.020, and 0.010, respectively. Thirty-three subjects (33.7{\%}) were heterozygous for *10/*1, and 18 (18.4{\%}) and 17 (17.3{\%}) subjects were homozygous for *1 and *10, respectively. Subjects who were homozygous for *10 showed the highest dextromethorphan MR among these 3 genotypes. Eighteen subjects (18.3{\%}) were heterozygous for *2, but their dextromethorphan MR values were not greater than the MR values of subjects who were homozygous for *1. One subject was a poor metabolizer phenotypically, and he was homozygous for *5. Conclusions: The CΥP2D6 allele frequencies in our Japanese subjects differed from those determined in previous studies of white subjects or mainland Chinese subjects. Individuals homozygous for *10 who have relatively low in vivo CΥP2D6 activity represent almost 20{\%} of the Japanese population. In addition, we did not identify any subjects with amplified *2 among our 98 Japanese men.",
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T1 - Analysis of the CΥP2D6 gene in relation to dextromethorphan O- demethylation capacity in a Japanese population

AU - Tateishi, Tomonori

AU - Chida, Michihiro

AU - Ariyoshi, Noritaka

AU - Mizorogi, Yoshihiro

AU - Kamataki, Tetsuya

AU - Kobayashi, Shinichi

PY - 1999

Y1 - 1999

N2 - Objective: To analyze the CΥP2D6 allele frequencies in a Japanese population and to evaluate the effects of CΥP2D6 variants on in vivo CΥP2D6 activity as measured by the dextromethorphan metabolic ratio (MR). Method: Ninety-eight unrelated, healthy Japanese men were phenotyped with dextromethorphan and genotyped by the polymerase chain reaction amplification method for 7 CΥP2D6 alleles. Results: The CΥP2D6*1, CΥP2D6*10, CΥP2D6*2, CΥP2D6*5, CΥP2D6*4, and CΥP2D6*21 allele frequencies in our Japanese subjects were 0.423, 0.408, 0.092, 0.061, 0.020, and 0.010, respectively. Thirty-three subjects (33.7%) were heterozygous for *10/*1, and 18 (18.4%) and 17 (17.3%) subjects were homozygous for *1 and *10, respectively. Subjects who were homozygous for *10 showed the highest dextromethorphan MR among these 3 genotypes. Eighteen subjects (18.3%) were heterozygous for *2, but their dextromethorphan MR values were not greater than the MR values of subjects who were homozygous for *1. One subject was a poor metabolizer phenotypically, and he was homozygous for *5. Conclusions: The CΥP2D6 allele frequencies in our Japanese subjects differed from those determined in previous studies of white subjects or mainland Chinese subjects. Individuals homozygous for *10 who have relatively low in vivo CΥP2D6 activity represent almost 20% of the Japanese population. In addition, we did not identify any subjects with amplified *2 among our 98 Japanese men.

AB - Objective: To analyze the CΥP2D6 allele frequencies in a Japanese population and to evaluate the effects of CΥP2D6 variants on in vivo CΥP2D6 activity as measured by the dextromethorphan metabolic ratio (MR). Method: Ninety-eight unrelated, healthy Japanese men were phenotyped with dextromethorphan and genotyped by the polymerase chain reaction amplification method for 7 CΥP2D6 alleles. Results: The CΥP2D6*1, CΥP2D6*10, CΥP2D6*2, CΥP2D6*5, CΥP2D6*4, and CΥP2D6*21 allele frequencies in our Japanese subjects were 0.423, 0.408, 0.092, 0.061, 0.020, and 0.010, respectively. Thirty-three subjects (33.7%) were heterozygous for *10/*1, and 18 (18.4%) and 17 (17.3%) subjects were homozygous for *1 and *10, respectively. Subjects who were homozygous for *10 showed the highest dextromethorphan MR among these 3 genotypes. Eighteen subjects (18.3%) were heterozygous for *2, but their dextromethorphan MR values were not greater than the MR values of subjects who were homozygous for *1. One subject was a poor metabolizer phenotypically, and he was homozygous for *5. Conclusions: The CΥP2D6 allele frequencies in our Japanese subjects differed from those determined in previous studies of white subjects or mainland Chinese subjects. Individuals homozygous for *10 who have relatively low in vivo CΥP2D6 activity represent almost 20% of the Japanese population. In addition, we did not identify any subjects with amplified *2 among our 98 Japanese men.

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