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Title: HLA-B*13:01 and the dapsone hypersensitivity syndrome
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. 
Issue Date: 2013
Citation: 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. (2013). HLA-B*13:01 and the dapsone hypersensitivity syndrome. New England Journal of Medicine 369 (17) : 1620-1628. ScholarBank@NUS Repository.
Abstract: 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). HLAB*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. Copyright © 2013 Massachusetts Medical Society.
Source Title: New England Journal of Medicine
ISSN: 00284793
DOI: 10.1056/NEJMoa1213096
Appears in Collections:Staff Publications

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