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Effect of polygenic load on striatal dopaminergic deterioration in Parkinson disease

Authors
 Myung Jun Lee  ;  Kyoungjune Pak  ;  Jong Hun Kim  ;  Yun Joong Kim  ;  Jeehee Yoon  ;  Jinwoo Lee  ;  Chul Hyoung Lyoo  ;  Hyung Jun Park  ;  Jae-Hyeok Lee  ;  Na-Yeon Jung 
Citation
 NEUROLOGY, Vol.93(7) : e665-e674, 2019 
Journal Title
 NEUROLOGY 
ISSN
 0028-3878 
Issue Date
2019
MeSH
Adult ; Aged ; Caudate Nucleus/metabolism ; Corpus Striatum/metabolism* ; Disease Progression ; Dopamine Plasma Membrane Transport Proteins/metabolism ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/complications ; Parkinson Disease/genetics ; Parkinson Disease/metabolism* ; Parkinsonian Disorders/complications ; Parkinsonian Disorders/metabolism* ; Putamen/metabolism ; Tropanes/metabolism*
Abstract
OBJECTIVE: To investigate the effect of polygenic load on the progression of striatal dopaminergic dysfunction in patients with Parkinson disease (PD). METHODS: Using data from 335 patients with PD in the Parkinson's Progression Markers Initiative (PPMI) database, we investigated the longitudinal association of PD-associated polygenic load with changes in striatal dopaminergic activity as measured by 123I-N-3-fluoropropyl-2-β-carboxymethoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT over 4 years. PD-associated polygenic load was estimated by calculating weighted genetic risk scores (GRS) using 1) all available 27 PD-risk single nucleotide polymorphisms (SNPs) in the PPMI database (GRS1) and 2) 23 SNPs with minor allele frequency >0.05 (GRS2). RESULTS: GRS1 and GRS2 were correlated with younger age at onset in patients with PD (GRS1, Spearman ρ = -0.128, p = 0.019; GRS2, Spearman ρ = -0.109, p = 0.047). Although GRS1 did not show an association with changes in striatal 123I-FP-CIT availability, GRS2 was associated with a slower decline of striatal dopaminergic activity (interactions with disease duration in linear mixed model; caudate nucleus, estimate = 0.399, SE = 0.165, p = 0.028; putamen, estimate = 0.396, SE = 0.137, p = 0.016). CONCLUSIONS: Our results suggest that genetic factors for PD risk may have heterogeneous effects on striatal dopaminergic degeneration, and some factors may be associated with a slower decline of dopaminergic activity. Composition of PD progression-specific GRS may be useful in predicting disease progression in patients.
Full Text
https://n.neurology.org/content/93/7/e665.long
DOI
10.1212/WNL.0000000000007939
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174494
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