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Title: Genetic Association of Co-Trimoxazole-Induced Severe Cutaneous Adverse Reactions Is Phenotype-Specific: HLA Class I Genotypes and Haplotypes
Authors: Chonlaphat Sukasem
Jirawat Pratoomwun
Patompong Satapornpong
Jettanong Klaewsongkram
Ticha Rerkpattanapipat
Pawinee Rerknimitr
Pattamon Lertpichitkul
Apichaya Puangpetch
Nontaya Nakkam
Parinya Konyoung
Usanee Khunarkornsiri
Wareeporn Disphanurat
Chutika Srisuttiyakorn
Oranuch Pattanacheewapull
Sirimas Kanjanawart
Thachanan Kongpan
Pansu Chumworathayi
Niwat Saksit
Jackrapong Bruminhent
Wichittra Tassaneeyakul
Wasun Chantratita
Munir Pirmohamed
Liverpool University Hospitals NHS Foundation Trust
University of Phayao
Udon Thani Center Hospital
Chulalongkorn University
Rangsit University
King Chulalongkorn Memorial Hospital, Faculty of Medicine Chulalongkorn University
Khon Kaen University
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Khon Kaen Regional Hospital
Thammasat University
Phramongkutklao College of Medicine
The Thai Severe Cutaneous Adverse Drug Reaction (THAI-SCAR) Research Group
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2020
Citation: Clinical Pharmacology and Therapeutics. (2020)
Abstract: © 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics Co-trimoxazole (CTX) causes various forms of severe cutaneous adverse reactions (SCARs). This case-control study was conducted to investigate the involvement between genetic variants of human leukocyte antigen (HLA) and CYP2C9 in CTX-induced SCARs, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) in Thai patients. Thirty cases of CTX-induced SCARs were enrolled and compared with 91 CTX-tolerant controls and 150 people from the general Thai population. Cases comprised 18 SJS/TEN and 12 DRESS patients. This study demonstrated that genetic association of CTX-induced SCARs was phenotype-specific. HLA-B*15:02 and HLA-C*08:01 alleles were significantly associated with CTX-induced SJS/TEN, whereas the HLA-B*13:01 allele was significantly associated with CTX-induced DRESS. In addition, a significant higher frequency of HLA-A*11:01-B*15:02 and HLA-B*13:01-C*03:04 haplotypes were detected in the group of CTX-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and DRESS cases, respectively. Genetic association of CTX-induced SCARs is phenotype-specific. Interestingly, these association was observed only in HIV-infected patients but not in non-HIV-infected patients.
ISSN: 15326535
Appears in Collections:Scopus 2020

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