HLA-A*31: 01 and HLA-B*15:02 association with Stevens–Johnson syndrome and toxic epidermal necrolysis to carbamazepine in a multiethnic Malaysian population

The majority of the carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis CBZ-SJS/TEN are associated with HLA-B*15:02 in Asian populations where this allele is common. In contrast, the association with HLA-A*31:01 is only reported in Japanese and Europeans. This study aimed to further investigate the association with HLA-A*31:01 besides HLA-B*15:02 in a multiethnic Malaysian population. Twenty-eight CBZ-SJS/TEN cases and 227 CBZ-tolerant controls were recruited. Association was tested by comparing carrier frequencies of the alleles between cases and controls. Significant associations were detected between HLA-B*15:02 and CBZ-SJS/TEN in independent ethnic groups: Malays [P=2.00×10−8; odds ratio (OR): 49.0; 95% confidence interval (CI): 9.36–256.81], Chinese (P=0.0047; OR: 14.3; 95% CI: 2.38–86.03) and Indians (P=0.04; OR: 13.8; 95% CI: 1.51–124.99). Combined analysis of all ethnic groups showed a significant association with OR Cochran–Mantel–Haenszel (ORCMH) of 26.6 (95% CI: 12.80–55.25; PCMH=2.31×10−26). In Indians, HLA-A*31:01 was found to be associated significantly with CBZ-SJS/TEN (P=0.023; OR: 10.4; 95% CI: 1.64–65.79) and combined analyses of both variants, HLA-A*31:01 and HLA-B*15:02, increased the strength of the association (P=0.0068; OR: 14.3; 95% CI: 2.20–92.9). Besides HLA-B*15:02, our study found a new association between HLA-A*31:01 and CBZ-SJS/TEN in Indians.

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