title: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Supharat
authors.initials: S
authors.lastname: Suvichapanich
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Jiraphun
authors.initials: J
authors.lastname: Jittikoon
authors.affiliation: Medical Genetic Centre, Medical Life Science Institute, Department of Medical Science, Ministry of Public Health, Nontaburi, Thailand.
authors.forename: Nuanjun
authors.initials: N
authors.lastname: Wichukchinda
authors.affiliation: Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Wasu
authors.initials: W
authors.lastname: Kamchaisatian
authors.affiliation: Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Anannit
authors.initials: A
authors.lastname: Visudtibhan
authors.affiliation: Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Suwat
authors.initials: S
authors.lastname: Benjapopitak
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors.forename: Somjai
authors.initials: S
authors.lastname: Nakornchai
authors.affiliation: Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Wiparat
authors.initials: W
authors.lastname: Manuyakorn
authors.affiliation: Medical Genetic Centre, Medical Life Science Institute, Department of Medical Science, Ministry of Public Health, Nontaburi, Thailand.
authors.forename: Surakameth
authors.initials: S
authors.lastname: Mahasirimongkol
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D003875:Drug Eruptions / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004827:Epilepsy / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000009:adverse effects* / Q000627:therapeutic use; D012720:Severity of Illness Index; D013785:Thailand / Q000453:epidemiology
chemical_list: D000927:Anticonvulsants; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9