Pediatric pharmacogenetics: profiling CYP2C8 polymorphisms at King Abdulaziz University Dental Clinic.

Abstract

Ibuprofen, a widely used non-steroidal anti-inflammatory (NSAID) for managing pain and inflammation in pediatric patients, is metabolized by the CYP2C8 enzyme. Studies suggest that the CYP2C8*2, *3, and *4 variations of the CYP2C8 gene diminish ibuprofen metabolism, increasing the risk of adverse reactions. The aim of this study was to determine the frequency of the CYP2C8*2, *3, and *4 alleles and genotypes in a pediatric population attending the King Abdulaziz University dental clinic and compare our findings to those of other populations. A cross-sectional study was conducted with 140 healthy Saudi children ages 6-12. Saliva samples were collected using Oragene™ DNA Sample Collection Kits and analyzed for polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The study identified that CYP2C8*2 AA, AT, and TT genotypes occurred at frequencies of 87.86 %, 9.29 %, and 2.86 %, respectively. For CYP2C8*3, AA, AG, and GG genotypes were found in 87.14 , 8.75, and 4.29 % of subjects, respectively. The CYP2C8*4 allele was less frequent, with CC and CG genotypes at 97.86 % and 2.14 %, respectively, and the GG genotype was absent. Allele frequencies for CYP2C8*2, *3, and *4 were 7.5 %, 8.57 %, and 1.07 %, respectively. Our findings reveal that the allelic frequencies for the CYP2C8 polymorphisms in the Saudi pediatric cohort are substantially elevated compared to those reported in other Asian populations. This suggests Saudis may experience more varied drug responses, especially for medications that undergo metabolism by the CYP2C8 enzyme, like ibuprofen.