Amino Acid Variants of HLA-DRB1 Confer Susceptibility to Dapsone Hypersensitivity Syndrome in Addition to HLA-B13:01
Amino Acid Variants of HLA-DRB1 Confer Susceptibility to Dapsone Hypersensitivity Syndrome in Addition to HLA-B13:01
复制标题
除了 HLA-B13:01 之外，HLA-DRB1 的氨基酸变体也导致对氨苯砜过敏综合征的易感性
DOI：
10.1016/j.jid.2017.11.027
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发表时间：
2018
影响因子：
6.5
通讯作者：
Zhang Furen
中科院分区：
文献类型：
--
作者：
Yue Zhenhua;Sun Yonghu;Wang Chuan;Yu Wenjun;Cao Jing;Bao Fangfang;Wang Zhenzhen;Liu Hong;Zhang Furen
氨苯砜超敏综合征（Dapsone hypersensitivity syndrome，DPS）是麻风病多药治疗的主要药物，是一种少见的严重药物不良反应，HLA-B*13：01是DPS的重要危险因素，但其阳性预测值较低，提示可能存在其他遗传变异。为了发现除HLA-B *13：01外的HLA基因座内的遗传变异，我们对中国人群中103例氨苯砜过敏和857例氨苯砜耐受的B*13：01阳性麻风患者进行了基于高覆盖率下一代测序（NGS）的HLA分型分析。HLA-DRB 1基因133、142、-17、11和13位氨基酸高度连锁不平衡突变与氨苯砜过敏综合征显著相关，其中DRB 1 *16：02和DRB 1 *15：01与氨苯砜过敏综合征的相关性在名义上显著。本研究鉴定了HLA-DRB 1内的5个氨基酸变异，它们处于高度连锁不平衡状态，与中国人群中的氨苯砜超敏综合征显著相关。
Dapsone hypersensitivity syndrome is a rare yet severe adverse drug reaction caused by dapsone, a principal drug in multidrug therapy for leprosy.HLA-B*13:01has been identified as a strong risk factor of dapsone hypersensitivity syndrome; however, its low positive predictive value indicated that additional genetic variants may be involved in the disease development. To discover contributing genetic variants within HLA loci in addition toHLA-B*13:01,we performed a high-coverage next-generation sequencing (NGS)–basedHLAtyping analysis in 103 dapsone-hypersensitive and 857 dapsone-tolerantHLA-B*13:01–positive leprosy patients in a Chinese population. Five amino acid variants in high linkage disequilibrium ofHLA-DRB1were significantly associated with dapsone hypersensitivity syndrome (positions 133, 142, –17, 11, and 13).DRB1*16:02andDRB1*15:01tagged by these risk-conferring amino acid residues were associated at a nominal significance level. This study identifies five amino acid variants withinHLA-DRB1that are in high linkage disequilibrium and significantly associated with dapsone hypersensitivity syndrome in a Chinese population.