HLA-B*13:01 与氨苯砜超敏反应综合征。
HLA-B*13:01 and the dapsone hypersensitivity syndrome.
机构信息
The authors' full names, degrees, and affiliations are listed in the Appendix.
出版信息
N Engl J Med. 2013 Oct 24;369(17):1620-8. doi: 10.1056/NEJMoa1213096.
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-B13:01 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-B13:01 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.).
背景
氨苯砜用于治疗感染和炎症性疾病。氨苯砜过敏综合征与报道的 9.9%的死亡率相关，约 0.5%至 3.6%接受该药物治疗的人会出现。目前，尚无测试可预测氨苯砜过敏综合征的风险。
方法
我们进行了一项全基因组关联研究，涉及 872 名接受氨苯砜作为麻风病多药治疗一部分的参与者（39 名出现氨苯砜过敏综合征，833 名对照），使用单核苷酸多态性（SNP）的对数加性测试和推断 HLA 分子。为了复制分析，我们对另外 31 名氨苯砜过敏综合征患者和 1089 名对照进行了 24 个 SNP 的基因分型，并在一组独立的 37 名氨苯砜过敏综合征患者和 201 名对照中进行了 HLA-B 和 HLA-C 的四代测序。
结果
全基因组关联分析表明，位于 HLA-B 和 MICA 基因座之间的 SNP rs2844573 与麻风病患者的氨苯砜过敏综合征显著相关（比值比，6.18；P=3.84×10(-13)）。HLA-B13:01 被确认为氨苯砜过敏综合征的危险因素（比值比，20.53；P=6.84×10(-25)）。HLA-B13:01 的存在作为氨苯砜过敏综合征的预测因子，其敏感性为 85.5%，特异性为 85.7%，其不存在使风险降低了 7 倍（从 1.4%降至 0.2%）。HLA-B*13:01 在中国人群中约占 2%至 20%，在日本人群中占 1.5%，在印度人群中占 1%至 12%，在东南亚人群中占 2%至 4%，但在欧洲人和非洲人中基本不存在。
结论
HLA-B*13:01 与麻风病患者氨苯砜过敏综合征的发生有关。（由国家自然科学基金等资助）。
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