CYP2C19 genotype and S-mephenytoin 4′-hydroxylation phenotype in a Chinese Dai population

Nan He, Feng Xiang Yan, Song Lin Huang, Wei Wang, Zhousheng Xiao, Zhao Qian Liu, Hong Hao Zhou

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Aims: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai population. Methods: One hundred and ninety-three healthy Chinese Dai volunteers were identified with respect to CYP2C19 by genotype and phenotype analyses. A polymerase chain reaction-restriction fragment length polymorphism method was performed for genotyping procedures. The 4′-hydroxymephenytoin (4′-OH-MP) and S/R-mephenytoin (S/R-MP) excreted in the urine were determined by high-performance liquid chromatography and gas chromatography, respectively. Results: Eighteen subjects were identified as poor metabolisers (PMs). The frequency of PMs in the Chinese Dai subjects was 9.3% (95% confidence interval 5.2, 13.4), which is lower than that in the Chinese Han population (P<0.05). Chinese Dai subjects had a higher frequency of the mutant CYP2C19*2 allele (0.303) and a lower frequency of the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all deficiencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of the CYP2C19*3 allele is significantly lower than that in the Chinese Han population (P<0.05). The mean S/R ratio was lower in the homozygous extensive metabolisers (EMs) compared with that in heterozygous EMs (P<0.01), and the latter was lower than that in the PMs (P<0.01). Furthermore, the mean S/R ratio in CYP2C19*3/CYP2C19*2 heterozygous PMs was possibly lower than that in the CYP2C19*2/CYP2C19*2 homozygous PMs (P<0.05). Conclusion: The frequencies of PMs and CYP2C19*3 allele in the Chinese Dai population are significantly lower than those in the Han population. The CYP2C19 genotype analysis is largely consistent with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and PMs shows a gene-dosage effect.

Original languageEnglish (US)
Pages (from-to)15-18
Number of pages4
JournalEuropean Journal of Clinical Pharmacology
Volume58
Issue number1
DOIs
StatePublished - Apr 27 2002

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Mephenytoin
Hydroxylation
Genotype
Phenotype
Population
Alleles
Cytochrome P-450 CYP2C19
Gene Dosage
Restriction Fragment Length Polymorphisms
Gas Chromatography

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

CYP2C19 genotype and S-mephenytoin 4′-hydroxylation phenotype in a Chinese Dai population. / He, Nan; Yan, Feng Xiang; Huang, Song Lin; Wang, Wei; Xiao, Zhousheng; Liu, Zhao Qian; Zhou, Hong Hao.

In: European Journal of Clinical Pharmacology, Vol. 58, No. 1, 27.04.2002, p. 15-18.

Research output: Contribution to journalArticle

He, Nan ; Yan, Feng Xiang ; Huang, Song Lin ; Wang, Wei ; Xiao, Zhousheng ; Liu, Zhao Qian ; Zhou, Hong Hao. / CYP2C19 genotype and S-mephenytoin 4′-hydroxylation phenotype in a Chinese Dai population. In: European Journal of Clinical Pharmacology. 2002 ; Vol. 58, No. 1. pp. 15-18.
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abstract = "Aims: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai population. Methods: One hundred and ninety-three healthy Chinese Dai volunteers were identified with respect to CYP2C19 by genotype and phenotype analyses. A polymerase chain reaction-restriction fragment length polymorphism method was performed for genotyping procedures. The 4′-hydroxymephenytoin (4′-OH-MP) and S/R-mephenytoin (S/R-MP) excreted in the urine were determined by high-performance liquid chromatography and gas chromatography, respectively. Results: Eighteen subjects were identified as poor metabolisers (PMs). The frequency of PMs in the Chinese Dai subjects was 9.3{\%} (95{\%} confidence interval 5.2, 13.4), which is lower than that in the Chinese Han population (P<0.05). Chinese Dai subjects had a higher frequency of the mutant CYP2C19*2 allele (0.303) and a lower frequency of the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all deficiencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of the CYP2C19*3 allele is significantly lower than that in the Chinese Han population (P<0.05). The mean S/R ratio was lower in the homozygous extensive metabolisers (EMs) compared with that in heterozygous EMs (P<0.01), and the latter was lower than that in the PMs (P<0.01). Furthermore, the mean S/R ratio in CYP2C19*3/CYP2C19*2 heterozygous PMs was possibly lower than that in the CYP2C19*2/CYP2C19*2 homozygous PMs (P<0.05). Conclusion: The frequencies of PMs and CYP2C19*3 allele in the Chinese Dai population are significantly lower than those in the Han population. The CYP2C19 genotype analysis is largely consistent with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and PMs shows a gene-dosage effect.",
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T1 - CYP2C19 genotype and S-mephenytoin 4′-hydroxylation phenotype in a Chinese Dai population

AU - He, Nan

AU - Yan, Feng Xiang

AU - Huang, Song Lin

AU - Wang, Wei

AU - Xiao, Zhousheng

AU - Liu, Zhao Qian

AU - Zhou, Hong Hao

PY - 2002/4/27

Y1 - 2002/4/27

N2 - Aims: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai population. Methods: One hundred and ninety-three healthy Chinese Dai volunteers were identified with respect to CYP2C19 by genotype and phenotype analyses. A polymerase chain reaction-restriction fragment length polymorphism method was performed for genotyping procedures. The 4′-hydroxymephenytoin (4′-OH-MP) and S/R-mephenytoin (S/R-MP) excreted in the urine were determined by high-performance liquid chromatography and gas chromatography, respectively. Results: Eighteen subjects were identified as poor metabolisers (PMs). The frequency of PMs in the Chinese Dai subjects was 9.3% (95% confidence interval 5.2, 13.4), which is lower than that in the Chinese Han population (P<0.05). Chinese Dai subjects had a higher frequency of the mutant CYP2C19*2 allele (0.303) and a lower frequency of the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all deficiencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of the CYP2C19*3 allele is significantly lower than that in the Chinese Han population (P<0.05). The mean S/R ratio was lower in the homozygous extensive metabolisers (EMs) compared with that in heterozygous EMs (P<0.01), and the latter was lower than that in the PMs (P<0.01). Furthermore, the mean S/R ratio in CYP2C19*3/CYP2C19*2 heterozygous PMs was possibly lower than that in the CYP2C19*2/CYP2C19*2 homozygous PMs (P<0.05). Conclusion: The frequencies of PMs and CYP2C19*3 allele in the Chinese Dai population are significantly lower than those in the Han population. The CYP2C19 genotype analysis is largely consistent with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and PMs shows a gene-dosage effect.

AB - Aims: To investigate the incidence of the CYP2C19 polymorphism in the Chinese Dai population. Methods: One hundred and ninety-three healthy Chinese Dai volunteers were identified with respect to CYP2C19 by genotype and phenotype analyses. A polymerase chain reaction-restriction fragment length polymorphism method was performed for genotyping procedures. The 4′-hydroxymephenytoin (4′-OH-MP) and S/R-mephenytoin (S/R-MP) excreted in the urine were determined by high-performance liquid chromatography and gas chromatography, respectively. Results: Eighteen subjects were identified as poor metabolisers (PMs). The frequency of PMs in the Chinese Dai subjects was 9.3% (95% confidence interval 5.2, 13.4), which is lower than that in the Chinese Han population (P<0.05). Chinese Dai subjects had a higher frequency of the mutant CYP2C19*2 allele (0.303) and a lower frequency of the mutant CYP2C19*3 allele (0.034). These two mutant alleles could explain all deficiencies of CYP2C19 activity in the Chinese Dai subjects. The frequency of the CYP2C19*3 allele is significantly lower than that in the Chinese Han population (P<0.05). The mean S/R ratio was lower in the homozygous extensive metabolisers (EMs) compared with that in heterozygous EMs (P<0.01), and the latter was lower than that in the PMs (P<0.01). Furthermore, the mean S/R ratio in CYP2C19*3/CYP2C19*2 heterozygous PMs was possibly lower than that in the CYP2C19*2/CYP2C19*2 homozygous PMs (P<0.05). Conclusion: The frequencies of PMs and CYP2C19*3 allele in the Chinese Dai population are significantly lower than those in the Han population. The CYP2C19 genotype analysis is largely consistent with the mephenytoin phenotype analysis. The variability of S/R ratios in EMs and PMs shows a gene-dosage effect.

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