계명대학교 의학도서관 Repository

HLAs associated with perampanel-induced psychiatric adverse effects in a Korean population

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Author(s)
Yoonhyuk JangTae-Joon KimJangsup MoonTae-Won YangKeun Tae KimByeong-Su ParkJung-Ah LimJin-Sun JunSoon-Tae LeeKeun-Hwa JungKyung-Il ParkKi-Young JungKon ChuSang Kun Lee
Keimyung Author(s)
Kim, Keun Tae
Department
Dept. of Neurology (신경과학)
Journal Title
Scientific Reports
Issued Date
2020
Volume
10
Issue
1
Abstract
Perampanel (PER) is a new-generation antiepileptic drug that has an occasional but significant shortcoming, psychiatric adverse effects (PAEs). Recently, antiepileptic drug-related adverse reactions, such as skin rash and even PAEs, have been discovered to be correlated with certain human leukocyte antigen (HLA) types. Thus, we aimed to analyze specific HLA alleles as risk factors for PER-PAEs. We prospectively enrolled 17 patients with epilepsy who were prescribed PER between May 2016 and Jul 2018 at Seoul National University Hospital and developed PAEs while taking PER. Their HLA types were analyzed compared to those of 19 patients in the PAE-tolerant group and the general Korean population. In silico docking was performed with two different computational programs, AutoDock Vina and SwissDock, to theoretically evaluate the binding affinity of PER in the grooves of the specific HLA alleles. The HLA-DQB1*06: 01, DRB1*08: 03, and B*54: 01 alleles were significantly associated with the patients who developed PER-PAEs compared with the general Korean population (odds ratio [OR] 3.94, p = 0.008, OR 9.24, p = 0.037, and OR 3.25, p = 0.041, respectively). As a haplotype, the combination of the three alleles was significantly more frequent in the PER-PAE group than in both the PER-tolerant group and the general Korean population. DQB1*06: 01 and B*54: 01 also demonstrated higher docking scores with PER than other alleles. This is the first study to analyze the association of PER-PAEs with specific HLA genotypes. Our results suggest that an HLA-associated genetic predisposition and a possible immunological mechanism are involved in the occurrence of PER-PAEs.
Keimyung Author(s)(Kor)
김근태
Publisher
School of Medicine (의과대학)
Citation
Yoonhyuk Jang et al. (2020). HLAs associated with perampanel-induced psychiatric adverse effects in a Korean population. Scientific Reports, 10(1), 13667. doi: 10.1038/s41598-020-70601-1
Type
Article
ISSN
2045-2322
Source
https://www.nature.com/articles/s41598-020-70601-1
DOI
10.1038/s41598-020-70601-1
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43296
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
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