PurposeTo determine genetic associations between antiseizure medications (ASMs)-induced maculopapular eruption (MPE) and human leukocyte antigen (HLA) variants in Xinjiang, China. MethodsA total of 409 patients were enrolled in this study, including 36 subjects with ASMs-induced MPE (case group) and 373 ASMs-tolerant patients (control group). We detected the whole sequence of the HLA alleles in the 409 Uighur patients using next-generation sequencing (NGS). The carried rate of HLA alleles were compared between the case group, the control group, and the general Chinese population. ResultsThe carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with both the ASMs-tolerant group (p = 0.000, odds ratio (OR) = 23.92, 95 % confidence interval (CI) = 3.96–74.84; p = 0.000, OR = 21.40, 95 % CI = 3.55–67.52; p = 0.030, OR = 4.69, 95 % CI = 0.90–61.73 and p = 0.000, OR = 18.94, 95 % CI = 3.15–60.58; respectively), and the general Chinese population (p = 0.000, OR = 21.34, 95 % CI = 3.31–38.98; p = 0.000, OR = 23.92, 95 % CI = 3.96–74.84; p = 0.019, OR = 5.53, 95 % CI = 0.14–19.86 and p = 0.000, OR = 21.67, 95 % CI = 3.68–11.73; respectively). Moreover, the carried rate of the HLA-B*4001 allele was significantly higher in the ASMs-tolerant group when compared with the ASMs-MPE group (p = 0.024, OR = 5.13, 95 % CI = 1.01–9.99). ConclusionsIn this study, we identified for the first time that the carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with the ASMs-tolerant group.