Analysis of the CYP2C19 polymorphism in a North-eastern Thai population.
CYP2C19 is a polymorphically expressed cytochrome P450 responsible for the metabolism of several clinically used drugs, including some barbiturates, diazepam, proguanil, propranolol and several proton pump inhibitors. Genetic polymorphism of this enzyme shows marked interracial differences, with the poor metabolizer (PM) phenotype representing 2-5% of Caucasian and 11-23% of Oriental populations. In the present study, CYP2C19 phenotype and genotype were investigated in 107 North-eastern Thai subjects using the omeprazole hydroxylation index (HI) and polymerase chain reaction-restriction fragment length polymorphism technique, respectively. It was found that the distribution of HI in these subjects was bimodal. Seven subjects [6.54%, 95% confidence (CI) 1.86-11.22%] were identified as PM, with an HI > 7. Analysis of CYP2C19 genotypes in these 107 Thai subjects revealed that the allele frequencies for CYP2C19*1, CYP2C19*2 and CYP2C19*3 were 0.71 (95% CI 0.65-0.77), 0.27 (95% CI 0.21-0.33) and 0.02 (95% CI 0.01-0.05), respectively. The PM phenotype and the frequencies of CYP2C19 defective alleles in Thais, particularly CYP2C19*3, were lower than those observed in other Oriental populations. It is noteworthy that there was a case of nonaccordance between phenotype and genotype in one of the PMs. Whether this PM represents a novel defective allele requires further investigation.
Tassaneeyakul
Wichittra
W
Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Thailand. wichit-t@md.kku.ac.th
Tawalee
Arporn
A
Tassaneeyakul
Wongwiwat
W
Kukongviriyapan
Veerapol
V
Blaisdell
Joyce
J
Goldstein
Joyce A
JA
Gaysornsiri
Dhanu
D
D000328:Adult; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D013785:Thailand / Q000208:ethnology
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole