Association analysis of CYP2C9∗3 and phenytoin-induced severe cutaneous adverse reactions (SCARs) in Thai epilepsy children

Abstract

CYP2C9 is the key enzyme in aromatic antiepileptic drugs (AEDs) metabolism. CYP2C9∗3 is a loss of function polymorphism. This study was designed to investigate genetic association between CYP2C9∗3 and aromatic AED-induced severe cutaneous adverse reactions (SCARs) in Thai children. The 37 aromatic AED-induced SCARs patients (20 phenobarbital and 17 phenytoin) and 35 tolerances (19 phenobarbital and 16 phenytoin) were enrolled. CYP2C9∗3 was genotyped by allele-specific PCRs. The association between CYP2C9∗3 with phenytoin-induced SCARs and phenobarbital-induced SCARs were analyzed in comparison with tolerances and healthy samples. Significant association between phenytoin-induced SCARs and CYP2C9∗3 was discovered (odds ratio=14.52; 95% confidence interval (CI)=1.18-∞, P-value=0.044). CYP2C9∗3 was not associated with phenobarbital-induced SCARs. This study is the first report of CYP2C9∗3 association to phenytoin-induced SCARs in Thai epileptic children. The CYP2C9∗3 is a reasonable predictive genetic marker to anticipate SCARs from phenytoin.