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 language | English |
|---|---|
| Pages (from-to) | 570-575 |
| Number of pages | 6 |
| Journal | Clinical Pharmacology and Therapeutics |
| Volume | 65 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 1999 |
| Externally published | Yes |
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- Pharmacology
Cite this
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 journal › Article
}
TY - JOUR
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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U2 - 10.1016/S0009-9236(99)70077-9
DO - 10.1016/S0009-9236(99)70077-9
M3 - Article
VL - 65
SP - 570
EP - 575
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
SN - 0009-9236
IS - 5
ER -