HLA-B51:01 is strongly associated with clindamycin-related cutaneous adverse drug reactions.
HLA-B51:01 is strongly associated with clindamycin-related cutaneous adverse drug reactions.
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HLA-B51:01 与克林霉素相关的皮肤药物不良反应密切相关。
DOI：
10.1038/tpj.2016.61
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Xing Q
中科院分区：
文献类型：
--
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
克林霉素引起皮肤药物不良反应（cADR），有时致病机制或风险因素未知。本研究旨在评估中国汉族人群中HLA等位基因是否与克林霉素相关cADR相关。我们对12例克林霉素相关cADR受试者、279例对照和26例克林霉素耐受受试者进行了相关性研究。单独分析静脉滴注克林霉素的受试者。进行了无偏倚的计算机模拟对接。12例克林霉素致cADR患者中6例携带HLA-B* 51：01，均静脉滴注克林霉素（6/9）。与对照组（P= 0.0006; OR= 9.731，95%CI：2.927-32.353）和克林霉素耐药组（OR= 24.000，95%CI：3.247-177.405）相比，HLA-B* 51：01携带率显著增高。计算机对接显示克林霉素在HLA-B* 51：01蛋白中可能更稳定。我们的研究结果首次表明，HLA-B* 51：01是汉族人群克林霉素相关cADR的危险等位基因，尤其是当克林霉素通过静脉滴注给药时。
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 clindamycin-tolerant 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.