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  • HLA-B13:01 and the dapsone hypersensitivity syndrome
    Zhang, F-R; Liu, H; Irwanto, A; Fu, X-A; Li, Y; Yu, G-Q; Yu, Y-X; Chen, M-F; Low, H-Q; Li, J-H; Bao, F-F; Foo, J-N; Bei, J-X; Jia, X-M; Liu, J; Liany, H; Wang, N; Niu, G-Y; Wang, Z-Z; Shi, B-Q; Tian, H-Q; Liu, H-X; Ma, S-S; Zhou, Y; You, J-B; Yang, Q; Wang, C; Chu, T-S; Liu, D-C; Yu, X-L; Sun, Y-H; Ning, Y; Wei, Z-H; Chen, S-L; Chen, X-C; Zhang, Z-X; Liu, Y-X; Pulit, S L; Wu, W-B; Zheng, Z-Y; Yang, R-D; Long, H; Liu, Z-S; Wang, J-Q; Li, M; Zhang, L-H; Wang, H; Wang, L-M; Xiao, P; Li, J-L; Huang, Z-M; Huang, J-X; Li, Z; Xiong, L; Yang, J; Wang, X-D; Yu, D-B; Lu, X-M; Zhou, G-Z; Yan, L-B; Shen, J-P; Zhang, G-C; Zeng, Y-X; de Bakker, P I W; Chen, S-M; Liu, J-J

    The New England journal of medicine, 10/2013, Volume: 369, Issue: 17
    Journal Article

    Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome. We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls. Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans. HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

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