HLA-B*13:01 and the dapsone hypersensitivity syndrome.
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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, Liu J, 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
Аннотация
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.).