부산대학교 도서관

Aim:To reveal the association of three class I HLAalleles, including HLA-A*33:03, HLA-B*58:01and HLA-C*03:02, and allopurinol-induced severe cutaneous adverse reactions (SCARs) in Vietnamese patients. Methods:A case–control study on 100 allopurinol-induced SCARs patients, 183 tolerant controls and 810 population controls was performed. The HLA-A*33:03and HLA-C*03:02alleles were detected with the nested allele-specific PCR method; the HLA-B*58:01allele was detected with the sequence-specific primer PCR method. Results:There were strong associations between HLA-B*58:01and HLA-C*03:02and allopurinol-induced SCARs. Specific associations were found between HLA-B*58:01and Stevens–Johnson syndrome/toxic epidermal necrolysis and between HLA-C*03:02and drug reaction with eosinophilia and systemic symptoms, with a gene dosage effect. The multivariate regression analysis indicated two significant independent risk factors: HLA-B*58:01/HLA-C*03:02and estimated glomerular filtration rate <60 ml/min/1.73 m2. The specificity, positive predictive value and negative predictive value of HLA-B*58:01testing were higher than the HLA-C*03:02or the multiplex testing, especially in patients with impaired renal function. Conclusion:The results supported pre-treatment HLA-B*58:01testing in Vietnamese patients with declined renal function to prevent SCARs.