Single nucleotide polymorphisms on CYP2C9 gene among Filipinos and its association with post-operative pain relief via COX-2 inhibitors.

Abstract

CYP2C9 gene encodes an enzyme involved in the metabolism of a wide variety of drugs which include celecoxib. This study investigated the frequencies of the alleles and genotypes of CYP2C9*1, CYP2C9*2, and CYP2C9*3 among Filipinos who underwent surgery, and to determine the association of CYP2C9 polymorphisms with post-operative pain relief via COX-2 inhibitors. Response to celecoxib was determined using the numerical rating scale (0-10) on the 24th and 48th hour of surgery. The CYP2C9 alleles were detected by real-time PCR. For CYP2C9*1 and CYP2C9*3, the allele frequencies among Filipinos were 99% and 1% respectively, which is similar with other East Asians. CYP2C9*2 alleles were not detected. The frequencies of CYP2C9*1/*1 and CYP2C9*1/*3 genotypes were 98% and 2% respectively. At 24 hours post-surgery, the average pain score was 2.57 ± 1.03, while on 48 hours post-surgery, the average pain score was 0.67 ± 0.61 among those who have the wild-type CYP2C9*1 allele. The average pain score on the 24th and 48th hour post-operatively was observed to be 2.5 ± 0.71 and 0.5 ± 0.71 respectively among two patients classified as intermediate metabolizer carrying the CYP2C9*1/*3 genotype. Low frequencies of CYP2C9 polymorphisms were observed in the present study, this pattern was similar with other Asians except Indians, and considerably lower than Caucasians. Our results suggest that CYP2C9 genotyping is not routinely needed for Filipinos but must be considered among mixed races. Consequently, a more personalized therapeutic strategy was derived from these data, resulting in good clinical outcomes and less adverse drug effects.