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

The Pharmacogenomics Journal volume 17, pages 501–505 (2017)Cite this article

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Abstract

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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grants 81472873, 81071287 and 31371274), Science and Technology Commission of Shanghai Municipality (14DJ1400100), Scientific and Technological Research in Open Collaborative Projects of Henan Province (152106000044) and HHS|NIH|U.S. National Library of Medicine (4R00LM009826-03). We thank the patients for their cooperation. The work was done in Shanghai, China.

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Author notes

  1. J Xuan

    Present address: 10Current address: National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.,

  2. Y Yang and S Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Children’s Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    Y Yang, H Zhu, J Xuan, J Mu, L He & Q Xing

  2. Huashan Hospital, Fudan University, Shanghai, China

    S Chen, F Yang & X Luo

  3. Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China

    L Zhang

  4. Children’s Hospital Informatics Program, Boston, MA, USA

    G Alterovitz

  5. Center for Biomedical Informatics, Harvard Medical School, Boston, MA, USA

    G Alterovitz

  6. Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA

    G Alterovitz

  7. School of Pharmacy, Fudan University, Shanghai, China

    X Yang

  8. University of Arkansas at Little Rock/University of Arkansas for Medical Sciences Joint Bioinformatics Program, Little Rock, AR, USA

    H Luo

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Correspondence to X Luo or Q Xing.

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Yang, Y., Chen, S., Yang, F. et al. HLA-B*51:01 is strongly associated with clindamycin-related cutaneous adverse drug reactions. Pharmacogenomics J 17, 501–505 (2017). https://doi.org/10.1038/tpj.2016.61

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