Drugs Xagena
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.
Researchers 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, researchers 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, OR=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.
In conclusion, HLA-B*13:01 is associated with the development of the Dapsone hypersensitivity syndrome among patients with leprosy. ( Xagena )
Zhang F-R et al, N Engl J Med 2013; 369: 1620-1628
XagenaMedicine_2013
