HLA-B*13:01 and the dapsone hypersensitivity syndrome

Fu Ren Zhang; H. Liu; A. Irwanto; X. A. Fu; Y. Li; G. Q. Yu; Y. X. Yu; M. F. Chen; H. Q. Low; J. H. Li; F. F. Bao; J. N. Foo; J. X. Bei; X. M. Jia; J. Liu; H. Liany; N. Wang; G. Y. Niu; Z. Z. Wang; B. Q. Shi; H. Q. Tian; H. X. Liu; S. S. Ma; Y. Zhou; J. B. You; Q. Yang; C. Wang; T. S. Chu; D. C. Liu; X. L. Yu; Y. H. Sun; Y. Ning; Z. H. Wei; S. L. Chen; X. C. Chen; Z. X. Zhang; Y. X. Liu; S. L. Pulit; W. B. Wu; Z. Y. Zheng; R. D. Yang; H. Long; Z. S. Liu; J. Q. Wang; M. Li; L. H. Zhang; H. Wang; L. M. Wang; P. Xiao; J. L. Li; Z. M. Huang; J. X. Huang; Z. Li; J. Liu; L. Xiong; J. Yang; X. D. Wang; D. B. Yu; X. M. Lu; G. Z. Zhou; L. B. Yan; J. P. Shen; G. C. Zhang; Y. X. Zeng; P. I.W. De Bakker; S. M. Chen; J. J. Liu

doi:10.1056/NEJMoa1213096

HLA-B*13:01 and the dapsone hypersensitivity syndrome

Fu Ren Zhang^*, H. Liu, A. Irwanto, X. A. Fu, Y. Li, G. Q. Yu, Y. X. Yu, M. F. Chen, H. Q. Low, J. H. Li, F. F. Bao, J. N. Foo, J. X. Bei, X. M. Jia, J. Liu, H. Liany, N. Wang, G. Y. Niu, Z. Z. Wang, B. Q. ShiH. Q. Tian, H. X. Liu, S. S. Ma, Y. Zhou, J. B. You, Q. Yang, C. Wang, T. S. Chu, D. C. Liu, X. L. Yu, Y. H. Sun, Y. Ning, Z. H. Wei, S. L. Chen, X. C. Chen, Z. X. Zhang, Y. X. Liu, S. L. Pulit, W. B. Wu, Z. Y. Zheng, R. D. Yang, H. Long, Z. S. Liu, J. Q. Wang, M. Li, L. H. Zhang, H. Wang, L. M. Wang, P. Xiao, J. L. Li, Z. M. Huang, J. X. Huang, Z. Li, J. Liu, L. Xiong, J. Yang, X. D. Wang, D. B. Yu, X. M. Lu, G. Z. Zhou, L. B. Yan, J. P. Shen, G. C. Zhang, Y. X. Zeng, P. I.W. De Bakker, S. M. Chen, J. J. Liu

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	1620-1628
Number of pages	9
Journal	New England Journal of Medicine
Volume	369
Issue number	17
DOIs	https://doi.org/10.1056/NEJMoa1213096
Publication status	Published - 2013
Externally published	Yes

ASJC Scopus Subject Areas

General Medicine

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10.1056/NEJMoa1213096

Cite this

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, 369(17), 1620-1628. https://doi.org/10.1056/NEJMoa1213096

@article{961e3bb8cab54bbbaad52067207af5bb,

title = "HLA-B*13:01 and the dapsone hypersensitivity syndrome",

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.",

author = "Zhang, {Fu Ren} and H. Liu and A. Irwanto and Fu, {X. A.} and Y. Li 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 J. Liu and H. Liany and N. Wang 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 Y. Zhou and You, {J. B.} and Q. Yang and C. Wang and Chu, {T. S.} and Liu, {D. C.} and Yu, {X. L.} and Sun, {Y. H.} and Y. Ning 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 H. Long and Liu, {Z. S.} and Wang, {J. Q.} and M. Li and Zhang, {L. H.} and H. Wang and Wang, {L. M.} and P. Xiao and Li, {J. L.} and Huang, {Z. M.} and Huang, {J. X.} and Z. Li and J. Liu and L. Xiong and J. Yang 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 {De Bakker}, {P. I.W.} and Chen, {S. M.} and Liu, {J. J.}",

year = "2013",

doi = "10.1056/NEJMoa1213096",

language = "English",

volume = "369",

pages = "1620--1628",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "17",

}

Zhang, FR, Liu, H, Irwanto, A, Fu, XA, Li, Y, Yu, GQ, Yu, YX, Chen, MF, Low, HQ, Li, JH, Bao, FF, Foo, JN, Bei, JX, Jia, XM, Liu, J, Liany, H, Wang, N, Niu, GY, Wang, ZZ, Shi, BQ, Tian, HQ, Liu, HX, Ma, SS, Zhou, Y, You, JB, Yang, Q, Wang, C, Chu, TS, Liu, DC, Yu, XL, Sun, YH, Ning, Y, Wei, ZH, Chen, SL, Chen, XC, Zhang, ZX, Liu, YX, Pulit, SL, Wu, WB, Zheng, ZY, Yang, RD, Long, H, Liu, ZS, Wang, JQ, Li, M, Zhang, LH, Wang, H, Wang, LM, Xiao, P, Li, JL, Huang, ZM, Huang, JX, Li, Z, Liu, J, Xiong, L, Yang, J, Wang, XD, Yu, DB, Lu, XM, Zhou, GZ, Yan, LB, Shen, JP, Zhang, GC, Zeng, YX, De Bakker, PIW, Chen, SM & Liu, JJ 2013, 'HLA-B*13:01 and the dapsone hypersensitivity syndrome', New England Journal of Medicine, vol. 369, no. 17, pp. 1620-1628. https://doi.org/10.1056/NEJMoa1213096

TY - JOUR

T1 - HLA-B*13:01 and the dapsone hypersensitivity syndrome

AU - Zhang, Fu Ren

AU - Liu, H.

AU - Irwanto, A.

AU - Fu, X. A.

AU - Li, Y.

AU - Yu, G. Q.

AU - Yu, Y. X.

AU - Chen, M. F.

AU - Low, H. Q.

AU - Li, J. H.

AU - Bao, F. F.

AU - Foo, J. N.

AU - Bei, J. X.

AU - Jia, X. M.

AU - Liu, J.

AU - Liany, H.

AU - Wang, N.

AU - Niu, G. Y.

AU - Wang, Z. Z.

AU - Shi, B. Q.

AU - Tian, H. Q.

AU - Liu, H. X.

AU - Ma, S. S.

AU - Zhou, Y.

AU - You, J. B.

AU - Yang, Q.

AU - Wang, C.

AU - Chu, T. S.

AU - Liu, D. C.

AU - Yu, X. L.

AU - Sun, Y. H.

AU - Ning, Y.

AU - Wei, Z. H.

AU - Chen, S. L.

AU - Chen, X. C.

AU - Zhang, Z. X.

AU - Liu, Y. X.

AU - Pulit, S. L.

AU - Wu, W. B.

AU - Zheng, Z. Y.

AU - Yang, R. D.

AU - Long, H.

AU - Liu, Z. S.

AU - Wang, J. Q.

AU - Li, M.

AU - Zhang, L. H.

AU - Wang, H.

AU - Wang, L. M.

AU - Xiao, P.

AU - Li, J. L.

AU - Huang, Z. M.

AU - Huang, J. X.

AU - Li, Z.

AU - Liu, J.

AU - Xiong, L.

AU - Yang, J.

AU - Wang, X. D.

AU - Yu, D. B.

AU - Lu, X. M.

AU - Zhou, G. Z.

AU - Yan, L. B.

AU - Shen, J. P.

AU - Zhang, G. C.

AU - Zeng, Y. X.

AU - De Bakker, P. I.W.

AU - Chen, S. M.

AU - Liu, J. J.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84886265139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886265139&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1213096

DO - 10.1056/NEJMoa1213096

M3 - Article

C2 - 24152261

AN - SCOPUS:84886265139

SN - 0028-4793

VL - 369

SP - 1620

EP - 1628

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 17

ER -

HLA-B*13:01 and the dapsone hypersensitivity syndrome

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