1. Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population
- Author
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Wen-Hung Chung, Murad S, Hussein Sh, Too Cl, Ching Ching Ng, Siew Eng Choon, Chang Cc, Kheng Seang Lim, and Chun Kiat Lee
- Subjects
Male ,0301 basic medicine ,Phenytoin ,Pharmacogenomic Variants ,Population ,Genomics ,macromolecular substances ,HLA-B15 Antigen ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Gene Frequency ,Risk Factors ,Odds Ratio ,Genetics ,Humans ,Medicine ,Genetic Predisposition to Disease ,education ,Genetic Association Studies ,Malay ,Pharmacology ,education.field_of_study ,business.industry ,Malaysia ,language.human_language ,HLA-B ,Phenotype ,030104 developmental biology ,Drug development ,Pharmacogenetics ,Case-Control Studies ,Stevens-Johnson Syndrome ,Drug Hypersensitivity Syndrome ,Immunology ,language ,Molecular Medicine ,Anticonvulsants ,Female ,business ,Functional genomics ,030217 neurology & neurosurgery ,medicine.drug - 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.
- Published
- 2016
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