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

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

The New England journal of medicine (2013-10-25)

F-R 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

PMID24152261

ABSTRACT

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. 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. 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. 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.).

MATERIALS

Product Number

Brand

Product Description

A74807

Sigma-Aldrich

4-Aminophenyl sulfone, 97%

46158

Supelco

Dapsone, VETRANAL^®, analytical standard