HLA-B*51: 01 is strongly associated with clindamycin-related cutaneous adverse drug reactions

作者：Yang, Y.; Chen, S.; Yang, F.; Zhang, L.; Alterovitz, G.; Zhu, H.; Xuan, J.; Yang, X.; Luo, H.; Mu, J.; He, L.; Luo, X.^*; Xing, Q.^*

来源：The Pharmacogenomics Journal, 2017, 17(6): 501-505.

DOI：10.1038/tpj.2016.61

• INDUCED HYPERSENSITIVITY REACTIONS
• STEVENS-JOHNSON SYNDROME
• PROTEIN DATA-BANK
• CRYSTAL-STRUCTURES
• THAI POPULATION
• CARBAMAZEPINE
• ALLELE
• HLA-A-ASTERISK-3101
• INFECTIONS

Clindamycin causes cutaneous adverse drug reactions (cADRs), sometimes with the mechanisms of pathogenicity or risk factors unknown. This study aims to assess whether HLA alleles are associated with clindamycin-related cADRs in the Han Chinese population. We performed an association study of 12 subjects with clindamycin-related cADRs, 279 controls and 26 clindamycintolerant subjects. Subjects who received clindamycin through intravenous drip were analyzed separately. Unbiased, in silico docking was conducted. We found 6 out of 12 clindamycin-induced cADR patients carried HLA-B* 51: 01, and all of them received clindamycin via intravenous drip (6/9). The carrier frequency of HLA-B* 51: 01 is significantly higher compared with the control group (P=0.0006; OR = 9.731, 95% CI: 2.927-32.353) and the clindamycin-tolerant group (OR = 24.000, 95% CI: 3.247-177.405). In silico docking showed clindamycin is potentially more stable inside HLA-B* 51: 01 protein. Our results suggested, for the first time, that HLA-B* 51: 01 is a risk allele for clindamycin-related cADRs in Han Chinese, especially when clindamycin is administered via intravenous drip.

• 出版日期2017-12
• 单位复旦大学; 郑州大学