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HLA-B*13:01 and the Dapsone Hypersensitivity Syndrome
Open accessAbstract
BACKGROUND: 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. 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.).
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The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation
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Metadata
- Authors
- 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.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2013-10-24
- Volume
- 369
- Issue
- 17
- Pages
- 1620-1628
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2092786402
- Cited by
- 310
- References
- 16
- FWCI
- 11.08
- Type
- journal article
- Language
- en
- Open access
- bronze
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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., . . . Liu, J.-J. (2013). HLA-B*13:01 and the Dapsone Hypersensitivity Syndrome. New England Journal of Medicine. https://doi.org/10.1056/nejmoa1213096
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