title: HLA-B*51:01 is strongly associated with clindamycin-related cutaneous adverse drug reactions.
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.
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Children's Hospital Informatics Program, Boston, MA, USA.|Center for Biomedical Informatics, Harvard Medical School, Boston, MA, USA.|Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Alterovitz
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Xuan
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: University of Arkansas at Little Rock/University of Arkansas for Medical Sciences Joint Bioinformatics Program, Little Rock, AR, USA.
authors.forename: H
authors.initials: H
authors.lastname: Luo
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Mu
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: He
authors.affiliation: Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.affiliation: Children's Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Xing
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People; D002981:Clindamycin / Q000008:administration & dosage / Q000009:adverse effects*; D003198:Computer Simulation; D003875:Drug Eruptions / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059949:HLA-B51 Antigen / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D007262:Infusions, Intravenous; D062105:Molecular Docking Simulation; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D011485:Protein Binding
chemical_list: D000900:Anti-Bacterial Agents; D059949:HLA-B51 Antigen; D002981:Clindamycin