@article{24513,
  keywords = {Adult, Dapsone, Drug Hypersensitivity, Drug Therapy, Combination, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, genotype, HLA-B Antigens, Humans, Leprostatic Agents, leprosy, Male, Polymorphism, Single Nucleotide, Risk Factors, Sequence Analysis, DNA},
  author = {Zhang F-R and Liu H and Irwanto A and Fu X-A and Li Y and Yu G-Q and Yu Y-X and Chen M-F and Low H-Q and Li J-H and Bao F-F and Foo J-N and Bei J-X and Jia X-M and Liu J and Liany H and Wang N and Niu G-Y and Wang Z-Z and Shi B-Q and Tian H-Q and Liu H-X and Ma S-S and Zhou Y and You J-B and Yang Q and Wang C and Chu T-S and Liu D-C and Yu X-L and Sun Y-H and Ning Y and Wei Z-H and Chen S-L and Chen X-C and Zhang Z-X and Liu Y-X and Pulit S L and Wu W-B and Zheng Z-Y and Yang R-D and Long H and Liu Z-S and Wang J-Q and Li M and Zhang L-H and Wang H and Wang L-M and Xiao P and Li J-L and Huang Z-M and Huang J-X and Li Z and Liu J and Xiong L and Yang J and Wang X-D and Yu D-B and Lu X-M and Zhou G-Z and Yan L-B and Shen J-P and Zhang G-C and Zeng Y-X and Bakker P I W and Chen S-M and Liu J-J},
  title = {HLA-B*13:01 and the dapsone hypersensitivity syndrome.},
  abstract = {<p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.).</p>},
  year = {2013},
  journal = {The New England journal of medicine},
  volume = {369},
  pages = {1620-8},
  month = {2013 Oct 24},
  issn = {1533-4406},
  doi = {10.1056/NEJMoa1213096},
  language = {eng},
}