Genetic analysis of the S-mephenytoin polymorphism in a chinese population

Sonia M.F. de Morais, Joyce A. Goldstein, Hong Guang Xie, Song Ling Huang, Yi Qing Lu, Hui Xia, Zhousheng Xiao, Nan Ile, Hong Hao Zhou

Research output: Contribution to journalArticle

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Abstract

The 4'-hydroxylation of S-mephenytoin exhibits a polymorphism in humans, with the poor metabolizer phenotype exhibiting a lower frequency in white (3% to 5%) than in Oriental populations (13% to 23%). Two mutations in CYP2C19 (CYP2C19 m1 and CYP2C19 m2 ) have recently been described that account for ∼85% of white and 100% of Japanese poor metabolizers. This study examines whether these mutations account for the poor metabolizer phenotype in the Chinese population. The metabolism of S-mephenytoin exhibited a bimodal distribution in 244 unrelated Chinese subjects, although the distribution of the two phenotypes overlapped. In 75 selected Chinese subjects, CYP2C19 genotype analysis predicted the phenotype with 100% accuracy. The frequency of the poor metabolizer phenotype was ∼11% (95% confidence interval 7% to 15%). The frequency of the CYP2C19 m1 allele was 0.289, whereas that of CYP2C19 m2 was 0.044. Homozygous extensive metabolizers had slightly lower ratios of S R-mephenytoin compared with heterozygous extensive metabolizers, showing a gene-dosage effect. These data show the advantages of genotype analysis in investigations of the mephenytoin phenotype in Oriental subjects.

Original languageEnglish (US)
Pages (from-to)404-411
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume58
Issue number4
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Mephenytoin
Phenotype
Population
Genotype
Mutation
Gene Dosage
Hydroxylation
Cytochrome P-450 CYP2C19
Alleles
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

de Morais, S. M. F., Goldstein, J. A., Xie, H. G., Huang, S. L., Lu, Y. Q., Xia, H., ... Zhou, H. H. (1995). Genetic analysis of the S-mephenytoin polymorphism in a chinese population. Clinical Pharmacology and Therapeutics, 58(4), 404-411. https://doi.org/10.1016/0009-9236(95)90053-5

Genetic analysis of the S-mephenytoin polymorphism in a chinese population. / de Morais, Sonia M.F.; Goldstein, Joyce A.; Xie, Hong Guang; Huang, Song Ling; Lu, Yi Qing; Xia, Hui; Xiao, Zhousheng; Ile, Nan; Zhou, Hong Hao.

In: Clinical Pharmacology and Therapeutics, Vol. 58, No. 4, 01.01.1995, p. 404-411.

Research output: Contribution to journalArticle

de Morais, SMF, Goldstein, JA, Xie, HG, Huang, SL, Lu, YQ, Xia, H, Xiao, Z, Ile, N & Zhou, HH 1995, 'Genetic analysis of the S-mephenytoin polymorphism in a chinese population', Clinical Pharmacology and Therapeutics, vol. 58, no. 4, pp. 404-411. https://doi.org/10.1016/0009-9236(95)90053-5
de Morais, Sonia M.F. ; Goldstein, Joyce A. ; Xie, Hong Guang ; Huang, Song Ling ; Lu, Yi Qing ; Xia, Hui ; Xiao, Zhousheng ; Ile, Nan ; Zhou, Hong Hao. / Genetic analysis of the S-mephenytoin polymorphism in a chinese population. In: Clinical Pharmacology and Therapeutics. 1995 ; Vol. 58, No. 4. pp. 404-411.
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