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Clin Pharmacol Ther ; 108(5): 1078-1089, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32452529

RESUMO

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.


Assuntos
Antibacterianos/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/genética , Antígenos HLA/genética , Síndrome de Stevens-Johnson/genética , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/imunologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Infecções por HIV/imunologia , Antígenos HLA/imunologia , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/diagnóstico , Síndrome de Stevens-Johnson/imunologia , Tailândia , Adulto Jovem
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