Prevalence of Cyp2c9 Genetic Polymorphisms and Their Clinical Implications in Phenytoin-Treated Patients At A Regional Hospital in Indonesia

Abstract

Objective: This study aimed to determine the prevalence of cytochrome P450 2C9 (CYP2C9) polymorphisms and metabolic phenotypes among phenytoin-treated patients at Dr. Mohammad Zyn Sampang Regional General Hospital, Indonesia. Methods: A cross-sectional study was conducted involving 100 phenytoin-treated patients and 102 subjects in the population reference group. Genotyping of CYP2C9*2 and CYP2C9*3 was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Hardy–Weinberg equilibrium was evaluated using the chi-square (χ²) test, and associations between categorical variables were analyzed using Fisher’s exact test. A p-value<0.05 was considered statistically significant. Results: CYP2C9*2 was not detected in any subject. The CYP2C9*3 genotype distribution consisted of 66% wild type (*1/*1), 30% heterozygous mutant (*1/*3), and 4% homozygous mutant (*3/*3), corresponding to extensive, intermediate, and poor metabolizers, respectively. A significant association was observed between metabolic phenotype and seizure control (p = 0.006). Conclusion: The CYP2C9*3 polymorphism is present in the Madurese population and may significantly impact phenytoin treatment response. Implementing pharmacogenetic-guided therapy could improve both treatment safety and efficacy.