Amino Acid Variants of HLA-DRB1 Confer Susceptibility to Dapsone Hypersensitivity Syndrome in Addition to HLA-B*13:01

作者：Yue, Zhenhua; Sun, Yonghu; Wang, Chuan; Yu, Wenjun; Cao, Jing; Bao, Fangfang; Wang, Zhenzhen; Liu, Hong; Zhang, Furen^*

来源：Journal of Investigative Dermatology, 2018, 138(5): 1101-1106.

DOI：10.1016/j.jid.2017.11.027

• STEVENS-JOHNSON-SYNDROME
• EXPLAIN
• ASSOCIATIONS
• CHINESE
• ALLELE
• RISK
• MHC

Dapsone hypersensitivity syndrome is a rare yet severe adverse drug reaction caused by dapsone, a principal drug in multidrug therapy for leprosy. HLA-B*13:01 has 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 to HLA-B*13:01, we performed a high-coverage next-generation sequencing (NGS)-based HLA typing analysis in 103 dapsone-hypersensitive and 857 dapsone-tolerant HLA-B*13:01-positive leprosy patients in a Chinese population. Five amino acid variants in high linkage disequilibrium of HLA-DRB1 were significantly associated with dapsone hypersensitivity syndrome (positions 133, 142, -17, 11, and 13). DRB1*16:02 and DRB1*15:01 tagged by these risk-conferring amino acid residues were associated at a nominal significance level. This study identifies five amino acid variants within HLA-DRB1 that are in high linkage disequilibrium and significantly associated with dapsone hypersensitivity syndrome in a Chinese population.

• 出版日期2018-5
• 单位济南大学; 山东省立医院; 山东省医学科学院; 山东大学