Effect of CYP2C9*3 RS 1057910 Polymorphism on the Tolerability of Ibuprofen after Molar Tooth Extraction in Pakistani Population

Abstract

Post-extraction pain is frequently managed with ibuprofen, a widely used NSAID metabolized by CYP2C9. Genetic polymorphisms, particularly CYP2C9*3 rs1057910, may alter drug metabolism, influencing efficacy and tolerability. This study evaluated the impact of this variant on ibuprofen tolerability in a Pakistani population. A prospective observational study was conducted from August 2022 to August 2023 at Islamic International Medical College, Rawalpindi, and affiliated dental clinics. Two hundred adults undergoing unilateral molar extraction were enrolled. Standardized procedures were followed, and patients received ibuprofen 400 mg thrice daily for three days. Blood samples were collected for CYP2C9*3 genotyping. Adverse effects, especially gastropathy, were assessed on day four using the General Assessment of Side Effects (GASE) questionnaire. Associations between genotype and adverse effects were analyzed with Chi-square test. Allele frequencies were 82.8% (A) and 17.2% (C). The AA genotype was identified in 65.5% of participants, while 34.5% participants resulted in AC genotype. Adverse effects were significantly more common among AC carriers (43.5%) compared with AA carriers (16.8%) (p<0.001). The CYP2C9*3 rs1057910 polymorphism is associated with reduced ibuprofen tolerability in the Pakistani population, with heterozygous carriers showing a higher risk of gastropathy. These findings support the clinical relevance of pharmacogenetic screening to optimize NSAID prescribing and reduce adverse outcomes. Broader studies across diverse populations are recommended to validate these results and inform genotype-based dosing guidelines.