CYP2C19 genotype and S-mephenytoin 4'-hydroxylation phenotype in a Chinese Dai population.
OBJECTIVE
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).


CONCLUSIONS
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.
He
Nan
N
Pharmacogenetics Research Institute, Central South University, Changsha, Hunan 410078, China.
Yan
Feng-Xiang
FX
Huang
Song-Lin
SL
Wang
Wei
W
Xiao
Zhou-Sheng
ZS
Liu
Zhao-Qian
ZQ
Zhou
Hong-Hao
HH
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000378:metabolism* / Q000652:urine; D001189:Aryl Hydrocarbon Hydroxylases; D002681:China; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008617:Mephenytoin / Q000378:metabolism* / Q000652:urine; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D011110:Polymorphism, Genetic; D013237:Stereoisomerism
D000927:Anticonvulsants; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D008617:Mephenytoin