PMID- 32788606
OWN - NLM
STAT- MEDLINE
DCOM- 20210111
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 10
IP  - 1
DP  - 2020 Aug 12
TI  - HLAs associated with perampanel-induced psychiatric adverse effects in a Korean 
      population.
PG  - 13667
LID - 10.1038/s41598-020-70601-1 [doi]
LID - 13667
AB  - 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.
FAU - Jang, Yoonhyuk
AU  - Jang Y
AUID- ORCID: 0000-0002-3346-3357
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
FAU - Kim, Tae-Joon
AU  - Kim TJ
AUID- ORCID: 0000-0001-8451-6634
AD  - Department of Neurology, Ajou University School of Medicine, Suwon, South Korea.
FAU - Moon, Jangsup
AU  - Moon J
AUID- ORCID: 0000-0003-1282-4528
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
AD  - Rare Disease Center, Seoul National University Hospital, Seoul, South Korea.
FAU - Yang, Tae-Won
AU  - Yang TW
AD  - Department of Neurology, Gyeongsang National University Changwon Hospital, 
      Gyeongsang National University School of Medicine, Changwon, South Korea.
FAU - Kim, Keun Tae
AU  - Kim KT
AD  - Department of Neurology, Keimyung University Dongsan Medical Center, Daegu, South 
      Korea.
FAU - Park, Byeong-Su
AU  - Park BS
AD  - Department of Neurology, Ulsan University Hospital, Ulsan, South Korea.
FAU - Lim, Jung-Ah
AU  - Lim JA
AD  - Department of Neurology, Chamjoeun Hospital, Gwangju, South Korea.
FAU - Jun, Jin-Sun
AU  - Jun JS
AD  - Department of Neurology, Kangnam Sacred Heart Hospital, Hallym University College 
      of Medicine, Seoul, South Korea.
FAU - Lee, Soon-Tae
AU  - Lee ST
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
FAU - Jung, Keun-Hwa
AU  - Jung KH
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
FAU - Park, Kyung-Il
AU  - Park KI
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
AD  - Department of Neurology, Seoul National University Hospital Healthcare System 
      Gangnam Center, Seoul, South Korea.
FAU - Jung, Ki-Young
AU  - Jung KY
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
FAU - Chu, Kon
AU  - Chu K
AUID- ORCID: 0000-0001-5863-0302
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. stemcell.snu@gmail.com.
FAU - Lee, Sang Kun
AU  - Lee SK
AUID- ORCID: 0000-0003-1908-0699
AD  - Laboratory for Neurotherapeutics, Department of Neurology, Comprehensive Epilepsy 
      Center, Biomedical Research Institute, Seoul National University Hospital, 101 
      Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. sangkun2923@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200812
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Anticonvulsants)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (Nitriles)
RN  - 0 (Pyridones)
RN  - H821664NPK (perampanel)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anticonvulsants/*adverse effects
MH  - Drug-Related Side Effects and Adverse 
      Reactions/*epidemiology/etiology/metabolism/pathology
MH  - Epilepsy/*drug therapy/pathology/psychology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-DQ beta-Chains/*metabolism
MH  - Humans
MH  - Incidence
MH  - Male
MH  - Mental Disorders/*epidemiology/etiology/metabolism/pathology
MH  - Middle Aged
MH  - Nitriles
MH  - Pyridones/*adverse effects
MH  - Republic of Korea/epidemiology
MH  - Young Adult
PMC - PMC7423598
COIS- The authors declare no competing interests.
EDAT- 2020/08/14 06:00
MHDA- 2021/01/12 06:00
PMCR- 2020/08/12
CRDT- 2020/08/14 06:00
PHST- 2020/05/06 00:00 [received]
PHST- 2020/07/29 00:00 [accepted]
PHST- 2020/08/14 06:00 [entrez]
PHST- 2020/08/14 06:00 [pubmed]
PHST- 2021/01/12 06:00 [medline]
PHST- 2020/08/12 00:00 [pmc-release]
AID - 10.1038/s41598-020-70601-1 [pii]
AID - 70601 [pii]
AID - 10.1038/s41598-020-70601-1 [doi]
PST - epublish
SO  - Sci Rep. 2020 Aug 12;10(1):13667. doi: 10.1038/s41598-020-70601-1.