Cargando…
Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study
BACKGROUND: Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson's disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in...
Autores principales: | , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324346/ https://www.ncbi.nlm.nih.gov/pubmed/36852447 http://dx.doi.org/10.1111/cns.14135 |
_version_ | 1785069132392169472 |
---|---|
author | Wu, Jingjing Guo, Tao Zhou, Cheng Bai, Xueqin Liu, Xiaocao Gu, Luyan Xuan, Min Gu, Quanquan Huang, Peiyu Song, Zhe Zhang, Baorong Xu, Xiaojun Zhang, Minming Guan, Xiaojun |
author_facet | Wu, Jingjing Guo, Tao Zhou, Cheng Bai, Xueqin Liu, Xiaocao Gu, Luyan Xuan, Min Gu, Quanquan Huang, Peiyu Song, Zhe Zhang, Baorong Xu, Xiaojun Zhang, Minming Guan, Xiaojun |
author_sort | Wu, Jingjing |
collection | PubMed |
description | BACKGROUND: Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson's disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in PD. METHODS: Seventy‐four subjects, including 38 patients with PD and 36 age‐matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron‐related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted. RESULTS: Four strong SNP–QT associations were detected: rs602201‐susceptibility of bilateral SN, rs198440‐susceptibility of left SN, and rs7895403‐susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A− genotype of rs602201 and G allele/G− genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A− genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G− carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP‐by‐disease interaction in bilateral SN. CONCLUSIONS: This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of iron‐related pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic‐based. |
format | Online Article Text |
id | pubmed-10324346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103243462023-07-07 Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study Wu, Jingjing Guo, Tao Zhou, Cheng Bai, Xueqin Liu, Xiaocao Gu, Luyan Xuan, Min Gu, Quanquan Huang, Peiyu Song, Zhe Zhang, Baorong Xu, Xiaojun Zhang, Minming Guan, Xiaojun CNS Neurosci Ther Original Articles BACKGROUND: Dysfunction of iron metabolism, especially in substantia nigra (SN), is widely acknowledged in Parkinson's disease (PD), but the genetic influence on iron deposition remains largely unknown. Thus, in this study, we aimed to investigate potential genetic impacts on iron deposition in PD. METHODS: Seventy‐four subjects, including 38 patients with PD and 36 age‐matched normal controls, participated in this study. Imaging genetic association analysis was used to identify the specific influence of single nucleotide polymorphism (SNP) on iron‐related quantitative traits (QT). Genetic effects on iron deposition at the disease level, SNP level, and their interactive effect were highlighted. RESULTS: Four strong SNP–QT associations were detected: rs602201‐susceptibility of bilateral SN, rs198440‐susceptibility of left SN, and rs7895403‐susceptibility of left caudate head. Detailed analyses showed that: (1) significant iron deposition was exclusively found in bilateral SN in PD; (2) altered polymorphisms of the A allele/A− genotype of rs602201 and G allele/G− genotype of rs198440 and rs7895403 were more frequently observed in PD; (3) for rs602201, among all subjects, A− genotype carriers showed significantly increased iron content than TT genotype in bilateral SN; for rs198440 and rs7895403, G− carriers showed increased iron content than AA genotype in left SN and left caudate head, respectively; and (4) rs602201 exhibited significant SNP‐by‐disease interaction in bilateral SN. CONCLUSIONS: This study shows that rs602201 and rs198440 have a stimulative impact on nigral iron deposition in PD, which provides improved understanding of iron‐related pathogenesis in PD, and specifically, that vulnerability to iron deposition in SN is genetic‐based. John Wiley and Sons Inc. 2023-02-27 /pmc/articles/PMC10324346/ /pubmed/36852447 http://dx.doi.org/10.1111/cns.14135 Text en © 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wu, Jingjing Guo, Tao Zhou, Cheng Bai, Xueqin Liu, Xiaocao Gu, Luyan Xuan, Min Gu, Quanquan Huang, Peiyu Song, Zhe Zhang, Baorong Xu, Xiaojun Zhang, Minming Guan, Xiaojun Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study |
title | Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study |
title_full | Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study |
title_fullStr | Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study |
title_full_unstemmed | Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study |
title_short | Genetic impacts on nigral iron deposition in Parkinson's disease: A preliminary quantitative susceptibility mapping study |
title_sort | genetic impacts on nigral iron deposition in parkinson's disease: a preliminary quantitative susceptibility mapping study |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324346/ https://www.ncbi.nlm.nih.gov/pubmed/36852447 http://dx.doi.org/10.1111/cns.14135 |
work_keys_str_mv | AT wujingjing geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT guotao geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT zhoucheng geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT baixueqin geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT liuxiaocao geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT guluyan geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT xuanmin geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT guquanquan geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT huangpeiyu geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT songzhe geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT zhangbaorong geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT xuxiaojun geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT zhangminming geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy AT guanxiaojun geneticimpactsonnigralirondepositioninparkinsonsdiseaseapreliminaryquantitativesusceptibilitymappingstudy |