Genetic Association Of Co-Trimoxazole-Induced Severe Cutaneous Adverse Reactions Is Phenotype-Specific: Hla Class I Genotypes And Haplotypes

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) andCYP2C9in 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*15:02andHLA-C*08:01alleles were significantly associated with CTX-induced SJS/TEN, whereas theHLA-B*13:01allele was significantly associated with CTX-induced DRESS. In addition, a significant higher frequency ofHLA-A*11:01-B*15:02andHLA-B*13:01-C*03:04haplotypes 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.