TY - JOUR
KW - Adult
KW - Dapsone
KW - Drug Hypersensitivity
KW - Drug Therapy, Combination
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - genotype
KW - HLA-B Antigens
KW - Humans
KW - Leprostatic Agents
KW - leprosy
KW - Male
KW - Polymorphism, Single Nucleotide
KW - Risk Factors
KW - Sequence Analysis, DNA
AU - Zhang F-R
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 - Bakker P I W
AU - Chen S-M
AU - Liu J-J
AB - <p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.).</p>
BT - The New England journal of medicine
C1 - http://www.ncbi.nlm.nih.gov/pubmed/24152261?dopt=Abstract
CN - ZHANG 2013
DA - 2013 Oct 24
DO - 10.1056/NEJMoa1213096
IS - 17
J2 - N. Engl. J. Med.
LA - eng
N2 - <p><b>BACKGROUND: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.).</p>
PY - 2013
SP - 1620
EP - 8
T2 - The New England journal of medicine
TI - HLA-B*13:01 and the dapsone hypersensitivity syndrome.
VL - 369
SN - 1533-4406
ER -