| DOI: 10.29090/psa.2026.04.26.10771 | Pharm Sci Asia 2026; 53(4), 444-455 |
Prevalence of CYP2C9 polymorphisms and predicted metabolizer phenotypes in Balinese patients receiving phenytoin therapy at Buleleng Regency General Hospital, IndonesiaLenny Octaviana, Chrismawan Ardianto, Sudjarwo*
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Surabaya, East Java 60115, Indonesia
CYP2C9 polymorphisms contribute to interindividual variability in phenytoin metabolism, a medication characterized by a narrow therapeutic index. This study aimed to determine the prevalence of CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) polymorphisms and to classify CYP2C9 related predicted metabolizer phenotypes, namely Extensive Metabolizer (EM), Intermediate Metabolizer (IM), and Poor Metabolizer (PM), among Balinese patients receiving phenytoin therapy at Buleleng Regency General Hospital, Indonesia. A non-phenytoin Balinese group was included as a population reference comparator to describe the background distribution of CYP2C9 genetic variation. This observational cross-sectional study was conducted among 200 Balinese participants, consisting of 100 phenytoin users and 100 non-phenytoin participants as a population reference group. Genotyping of CYP2C9*2 and CYP2C9*3 was performed using the Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) method. Genotype and metabolizer phenotype distributions were analyzed descriptively, while differences in distribution between phenytoin users and non-phenytoin participants were evaluated using the Chi-square test. Among phenytoin users, no CYP2C9*2 polymorphism was detected, with all participants carrying the *1/*1 genotype. In contrast, CYP2C9*3 demonstrated greater genotype variability, with genotype frequencies of *1/*1 (41%), *1/*3 (42%), and *3/*3 (17%). Based on the variant-specific classification used in this study, these genotypes corresponded to the Extensive Metabolizer (EM), Intermediate Metabolizer (IM), and Poor Metabolizer (PM) phenotypes, respectively. No significant difference was observed in CYP2C9*3 genotype distribution or predicted metabolizer phenotype classification between phenytoin users and non-phenytoin participants (p = 0.739). CYP2C9*3 was the predominant decreased-function variant among Balinese participants receiving phenytoin therapy, whereas CYP2C9*2 was detected at a very low frequency and contributed minimally to CYP2C9 metabolic variability. The similar distribution of CYP2C9 genotypes and metabolizer phenotypes between phenytoin users and non-phenytoin participants suggests that the observed pattern likely reflects the underlying genetic characteristics of the Balinese population rather than the effect of phenytoin exposure. These findings provide pharmacogenetic baseline data on CYP2C9 distribution and predicted metabolizer phenotype variability, which may support future investigations evaluating phenytoin plasma concentrations and therapeutic response in the Balinese population.
Keyword:
CYP2C9; Phenytoin; Pharmacogenetics; Polymorphism; Metabolizer phenotype; Balinese; PCR-RFLP
Download full paper (PDF File size: 782.25 KB.)
|
