title: Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population.
abstract: Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
authors.affiliation: Department of Dermatology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
authors.forename: C-C
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Faculty of Science, Institute of Biological Sciences, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: C-C
authors.initials: CC
authors.lastname: Ng
authors.affiliation: Allergy and Immunology Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: C-L
authors.initials: CL
authors.lastname: Too
authors.affiliation: Department of Dermatology, Hospital Sultanah Aminah, Johor Bahru, Malaysia.
authors.forename: S-E
authors.initials: SE
authors.lastname: Choon
authors.affiliation: Pantai Hospital Cheras, Kuala Lumpur, Malaysia.
authors.forename: C-K
authors.initials: CK
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospitals, Taipei, Taiwan.
authors.forename: W-H
authors.initials: WH
authors.lastname: Chung
authors.affiliation: Department of Dermatology, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia.
authors.forename: S H
authors.initials: SH
authors.lastname: Hussein
authors.affiliation: Division of Neurology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: K-S
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Allergy and Immunology Research Center, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: S
authors.initials: S
authors.lastname: Murad
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects*; D016022:Case-Control Studies; D063926:Drug Hypersensitivity Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059910:HLA-B15 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008296:Malaysia; D008297:Male; D016017:Odds Ratio; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D010672:Phenytoin / Q000009:adverse effects*; D012307:Risk Factors; D012720:Severity of Illness Index; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology
chemical_list: D000927:Anticonvulsants; C483536:HLA-B*15:02 antigen; D059910:HLA-B15 Antigen; D010672:Phenytoin