| Abstract |
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain and inflammation, however, these drugs have been reported as one of the most common causative drugs of severe cutaneous adverse reactions (SCARs) including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reactions with eosinophilia and systemic symptoms (DRESS). Although the genetic polymorphisms of human leukocyte antigen (HLA) genes have been proposed as genetic factors of the development of drug-induced SCARs, the information on genetic markers for SCARs induced by NSAIDs is still limited. Therefore, this study aimed to determine the associations between HLA class I and II polymorphisms and NSAIDs-induced SCARs in Thai population. Sixteen patients with NSAIDs-induced SCARs, consisting of 15 SJS/TEN and 1 DRESS patients were enrolled in this study. All of NSAIDs-induced SCARs cases are Northeastern Thais. A control group was obtained from 183 unrelated healthy native Northeastern Thais who had no history of drug allergy. The HLA class I and II alleles were genotyped using the polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) method. The strength of associations was estimated by calculating the odds ratios (ORs) and 95% confidence intervals (CIs). The results showed that six HLA alleles including HLA-A*68:01, HLA-B*56:01, HLA-DQA1*01:01, HLA-DQA1*01:02, HLA-DQA1*03:01 and HLA-DQB1*03:02 were significantly associated with NSAIDs-induced SCARs. The odds ratios of NSAIDs-induced SCARs in the patients who carried one of these alleles ranged from 5.22- to 12.93-fold. The highest risk of SCARs was observed in patients with HLA-B*56:01 allele, which was 12.93-fold significantly higher compared with those who did not carry this allele (95% CI = 1.69-98.83, P-value = 0.0330), followed by the HLA-DQA1*01:01 allele and the HLA-A*68:01 allele. These findings demonstrated the candidate HLA alleles that could be valid pharmacogenetic markers for the prediction of SCARs induced by NSAIDs, however, these associations deserve further exploration in larger sample sizes and other ethnicities. |
Publication
Journal Publication
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