Genome-wide association study identifies zonisamide responsive gene in Parkinson's disease patients.
Aged
Antiparkinson Agents
/ pharmacology
Asian People
/ genetics
Cell Cycle Proteins
/ genetics
DNA-Binding Proteins
/ genetics
Female
Genome-Wide Association Study
Humans
Male
Middle Aged
Parkinson Disease
/ drug therapy
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins
/ genetics
Quantitative Trait Loci
Signal Transduction
/ genetics
Zonisamide
/ pharmacology
Journal
Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
03
02
2020
accepted:
31
03
2020
revised:
31
03
2020
pubmed:
2
5
2020
medline:
18
11
2020
entrez:
2
5
2020
Statut:
ppublish
Résumé
Long-term treatment of Parkinson's disease (PD) by levodopa leads to motor complication "wearing-off". Zonisamide is a nondopaminergic antiparkinsonian drug that can improve "wearing-off" although response to the treatment varies between individuals. To clarify the genetic basis of zonisamide responsiveness, we conducted a genome-wide association study (GWAS) on 200 PD patients from a placebo-controlled clinical trial, including 67 responders whose "off" time decreased ≥1.5 h after 12 weeks of zonisamide treatment and 133 poor responders. We genotyped and evaluated the association between 611,492 single nucleotide polymorphisms (SNPs) and "off" time reduction. We also performed whole-genome imputation, gene- and pathway-based analyses of GWAS data. For promising SNPs, we examined single-tissue expression quantitative trait loci (eQTL) data in the GTEx database. SNP rs16854023 (Mouse double minute 4, MDM4) showed genome-wide significant association with reduced "off" time (P
Identifiants
pubmed: 32355309
doi: 10.1038/s10038-020-0760-8
pii: 10.1038/s10038-020-0760-8
pmc: PMC8075945
doi:
Substances chimiques
Antiparkinson Agents
0
Cell Cycle Proteins
0
DNA-Binding Proteins
0
MDM4 protein, human
0
PDRG1 protein, human
0
Proto-Oncogene Proteins
0
Zonisamide
459384H98V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
693-704Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP17km0405206
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : 17ek0109207h0001
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 17H04056
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