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Genetic analysis of the S ‐mephenytoin polymorphism in a chinese population
Author(s) -
Morais Sonia M.F.,
Goldstein Joyce A.,
Xie HongGuang,
Huang SongLing,
Lu YiQing,
Xia Hui,
Xiao ZhouSheng,
Ile Nan,
Zhou HongHao
Publication year - 1995
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/0009-9236(95)90053-5
Subject(s) - mephenytoin , genotype , cyp2c19 , genetics , biology , polymorphism (computer science) , pharmacogenetics , phenotype , allele , debrisoquine , population , gene , medicine , environmental health
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 SR‐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. Clinical Pharmacology & Therapeutics (1995) 58 , 404–411; doi: