Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/24152261http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24152261http://www.w3.org/2000/01/rdf-schema#comment"

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.)."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.org/dc/terms/identifier"doi:10.1056/nejmoa1213096"xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Chen S.L."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Chen X.C."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Liu H."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Li Z."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Li J.H."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Li M."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Liu J.'"xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Liu Y.X."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Li J.L."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Wang C."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Yang J."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Yang Q."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Zhou Y."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Wang H."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Zeng Y.X."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Wang N."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Zhang L.H."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Xiong L."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Wang X.D."xsd:string
http://purl.uniprot.org/citations/24152261http://purl.uniprot.org/core/author"Ning Y."xsd:string
▶