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Dapsone-induced severe cutaneous adverse drug reactions are strongly linked with HLA-B*13: 01 allele in the Thai population

Tempark, Therdponga,*; Satapornpong, Patompongd,e,*; Rerknimitr, Pawineeb,h; Nakkam, Nontayai; Saksit, Niwati,k; Wattanakrai, Penpunf; Jantararoungtong, Thawineed,e; Koomdee, Napatruprond,e; Mahakkanukrauh, Ajaneej; Tassaneeyakul, Wichittrai; Suttisai, Sumitral; Pratoomwun, Jirawatd,e; Klaewsongkram, Jettanongc,h; Rerkpattanapipat, Tichag,h; Sukasem, Chonlaphatd,e,h

doi: 10.1097/FPC.0000000000000306
ORIGINAL ARTICLES
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Objectives A previous publication in Chinese leprosy patients showed that the HLA-B*13:01 allele is a strong genetic marker for dapsone-induced drug hypersensitivity reactions, however there are no data describing whether HLA-B*13:01 is a valid marker for prediction of dapsone-induced drug hypersensitivity reactions in other ethnicities or nonleprosy patients. The aim of this study is to investigate whether there is an association between HLA genotypes and dapsone-induced severe cutaneous adverse reactions (SCARs) in Thai nonleprosy patients.

Patients and methods HLA-B genotypes of 15 patients with dapsone-induced SCARs (11 drug reaction with eosinophilia and systemic symptoms, 4 Stevens–Johnson syndrome/toxic epidermal necrolysis), 29 control patients, and 986 subjects from the general Thai population were determined by the reverse PCR sequence-specific oligonucleotides probe.

Results The HLA-B*13:01 allele was significantly associated with dapsone-induced SCARs compared with dapsone-tolerant controls (odds ratio: 54.00, 95% confidence interval: 7.96–366.16, P=0.0001) and the general population (odds ratio: 26.11, 95% confidence interval: 7.27–93.75, P=0.0001). In addition, HLA-B*13:01 associated with dapsone-induced SJS-TEN (OR: 40.50, 95% confidence interval: 2.78-591.01, P=0.0070) and DRESS (OR: 60.75, 95% confidence interval: 7.44-496.18, P=0.0001).

Conclusion This study demonstrated an association between HLA-B*13:01 and dapsone-induced SCARs including Stevens–Johnson syndrome/toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms in nonleprosy patients. Moreover, these results suggest that the HLA-B*13:01 allele may be a useful genetic marker for prediction of dapsone-induced SCARs in Thai and Han-Chinese populations.

Departments of aPediatrics, Division of Pediatric Dermatology

bMedicine, Division of Dermatology, Skin and Allergy Research Unit

cMedicine, Division of Allergy and Clinical Immunology, Skin and Allergy Research Unit, Faculty of Medicine, Chulalongkorn University

dLaboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC)

eDepartment of Pathology, Division of Pharmacogenomics and Personalized Medicine

fDepartment of Medicine, Division of Dermatology

gDepartment of Medicine, Division of Allergy Immunology and Rheumatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University

hThe Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group, Bangkok

Departments of iPharmacology

jMedicine, Faculty of Medicine, Khon Kaen University, Khon Kaen

kSchool of Pharmaceutical Sciences, University of Phayao, Phayao

lPharmacy Department, Phrae Hospital, Phrae, Thailand

*Therdpong Tempark and Patompong Satapornpong contributed equally to the writing of this article.

Correspondence to Chonlaphat Sukasem, B.Pharm, PhD, Department of Pathology, Division of Pharmacogenetics and Personalized Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand Tel: +66 220 04331; fax: +66 220 04332; e-mail: chonlaphat.suk@mahidol.ac.th

Received December 18, 2016

Accepted May 21, 2017

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