title: HLA-B (*) 58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand.
abstract: BACKGROUND
  The aim of this study was to investigate the predisposition to different types of allopurinol-induced cutaneous adverse drug reactions (CADR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN; SJS-TEN, n = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, n = 10) and Maculopapular eruption (MPE; n = 7), conferred by HLA-B (*) 58:01 in a Thai population.
  
  
  METHODS
  This case-control association study compares 30 patients with allopurinol-induced CADR, allopurinol-tolerant control patients (n = 100), and a Thai general population (n = 1095). Patients' human leukocyte antigen type B (HLA-B) alleles were genotyped by using a two-stage sequence-specific oligonucleotide probe system.
  
  
  RESULTS
  Of a total 30 patients with CADR due to allopurinol, 29 (96.7%) patients were found to be at least heterozygous for HLA-B (*) 58:01, compared to only 4.0% in allopurinol-tolerant patients (p < 0.001). Odds ratio (OR) for the association of HLA-B (*) 58:01 with allopurinol-induced CADR in this population was 696.0 (95% CI: 74.8-6475.0). The HLA-B (*) 58:01 allele was present in all patients with allopurinol-induced SJS-TEN (OR = 579.0, 95%CI: 29.5-11362.7, p < 0.001) and DRESS (OR 430.3, 95%CI: 22.6-8958.9, p < 0.001). Additionally, OR of HLA-B (*) 58:01 was highly significant in the allopurinol-induced MPE patients (OR 144.0, 95%CI: 13.9-1497.0, p < 0.001).
  
  
  CONCLUSIONS
  In this study we confirmed the association between HLAB (*) 58:01 and allopurinol-induced SJS-TEN in a Thai population. In addition, we identified an association between HLA-B (*) 58:01 and allopurinol-induced DRESS and MPE in this population. Therefore, HLA-B (*) 58:01 can be used as a pharmacogenetic marker for allopurinol-induced CADR including SJS-TEN, DRESS and MPE. These results suggest that screening for HLA-B (*) 58:01 alleles in patients who will be treated with allopurinol would be clinically helpful in preventing the risk of developing CARD in a Thai patients. Summary Regardless of phenotype, this is the first pharmacogenetic study of allopurinol-induced CADR in patients of Thai ancestry.In this study we confirmed the association between HLA-B (*) 58:01 and allopurinol-induced SJS-TEN, DRESS, and MPE in Thai population.Regarding to our findings, the pharmacogenetic interpretation could be generalized to drug hypersensitivity including DRESS, SJS-TEN, and MPE.
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand; The Thai Severe Cutaneous Adverse Drug Reaction Research GroupBangkok, Thailand.
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Thawinee
authors.initials: T
authors.lastname: Jantararoungtong
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University Bangkok, Thailand.
authors.forename: Parnrat
authors.initials: P
authors.lastname: Kuntawong
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Apichaya
authors.initials: A
authors.lastname: Puangpetch
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi HospitalBangkok, Thailand.
authors.forename: Napatrupron
authors.initials: N
authors.lastname: Koomdee
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University Bangkok, Thailand.
authors.forename: Patompong
authors.initials: P
authors.lastname: Satapornpong
authors.affiliation: Department of Pharmacy, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital Bangkok, Thailand.
authors.forename: Patcharin
authors.initials: P
authors.lastname: Supapsophon
authors.affiliation: The Thai Severe Cutaneous Adverse Drug Reaction Research GroupBangkok, Thailand; Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Allergy and Clinical Immunology Research Group, Chulalongkorn UniversityBangkok, Thailand.
authors.forename: Jettanong
authors.initials: J
authors.lastname: Klaewsongkram
authors.affiliation: The Thai Severe Cutaneous Adverse Drug Reaction Research GroupBangkok, Thailand; Division of Allergy Immunology and Rheumatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityBangkok, Thailand.
authors.forename: Ticha
authors.initials: T
authors.lastname: Rerkpattanapipat
keywords: DRESS; HLA-B*58:01; MPE; SJS; TEN; Thai; allopurinol; drug hypersensitivity