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Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease

BACKGROUND: Inflammation and oxidative stress are recognized as important contributors to Parkinson’s disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for the disease as well as in the treatment outcome. Dopaminergic treatment is effective in m...

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Autores principales: Redenšek, Sara, Flisar, Dušan, Kojović, Maja, Kramberger, Milica Gregorič, Georgiev, Dejan, Pirtošek, Zvezdan, Trošt, Maja, Dolžan, Vita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393982/
https://www.ncbi.nlm.nih.gov/pubmed/30813952
http://dx.doi.org/10.1186/s12974-019-1439-y
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author Redenšek, Sara
Flisar, Dušan
Kojović, Maja
Kramberger, Milica Gregorič
Georgiev, Dejan
Pirtošek, Zvezdan
Trošt, Maja
Dolžan, Vita
author_facet Redenšek, Sara
Flisar, Dušan
Kojović, Maja
Kramberger, Milica Gregorič
Georgiev, Dejan
Pirtošek, Zvezdan
Trošt, Maja
Dolžan, Vita
author_sort Redenšek, Sara
collection PubMed
description BACKGROUND: Inflammation and oxidative stress are recognized as important contributors to Parkinson’s disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson’s disease susceptibility and the occurrence of adverse events of dopaminergic treatment. METHODS: In total, 224 patients were enrolled, and their demographic and clinical data on the disease course were collected. Furthermore, a control group of 146 healthy Slovenian blood donors were included for Parkinson’s disease’ risk evaluation. Peripheral blood was obtained for DNA isolation. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1β rs16944, IL1β rs1143623, IL6 rs1800795, CAT rs1001179, CAT rs10836235, SOD2 rs4880, NOS1 rs2293054, NOS1 rs2682826, TNF-α rs1800629, and GPX1 rs1050450. Logistic regression was used for analysis of possible associations. RESULTS: We observed a nominally significant association of the IL1β rs1143623 C allele with the risk for Parkinson’s disease (OR = 0.59; 95%CI = 0.38–0.92, p = 0.021). CAT rs1001179 A allele was significantly associated with peripheral edema (OR = 0.32; 95%CI = 0.15–0.68; p = 0.003). Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00–3.06, p = 0.048), SOD2 rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25–0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32–1.00, p = 0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09–6.19; p = 0.032). We did not find any associations between selected polymorphisms and motor adverse events. CONCLUSIONS: Apart from some nominally significant associations, one significant association between CAT genetic variability and peripheral edema was observed as well. Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment. However, the investigated polymorphisms do not play a major role in the occurrence of the disease and the adverse events of dopaminergic treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1439-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-63939822019-03-11 Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease Redenšek, Sara Flisar, Dušan Kojović, Maja Kramberger, Milica Gregorič Georgiev, Dejan Pirtošek, Zvezdan Trošt, Maja Dolžan, Vita J Neuroinflammation Research BACKGROUND: Inflammation and oxidative stress are recognized as important contributors to Parkinson’s disease pathogenesis. As such, genetic variability in these pathways could have a role in susceptibility for the disease as well as in the treatment outcome. Dopaminergic treatment is effective in management of motor symptoms, but poses a risk for motor and non-motor adverse events. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in genes involved in inflammation and oxidative stress on Parkinson’s disease susceptibility and the occurrence of adverse events of dopaminergic treatment. METHODS: In total, 224 patients were enrolled, and their demographic and clinical data on the disease course were collected. Furthermore, a control group of 146 healthy Slovenian blood donors were included for Parkinson’s disease’ risk evaluation. Peripheral blood was obtained for DNA isolation. Genotyping was performed for NLRP3 rs35829419, CARD8 rs2043211, IL1β rs16944, IL1β rs1143623, IL6 rs1800795, CAT rs1001179, CAT rs10836235, SOD2 rs4880, NOS1 rs2293054, NOS1 rs2682826, TNF-α rs1800629, and GPX1 rs1050450. Logistic regression was used for analysis of possible associations. RESULTS: We observed a nominally significant association of the IL1β rs1143623 C allele with the risk for Parkinson’s disease (OR = 0.59; 95%CI = 0.38–0.92, p = 0.021). CAT rs1001179 A allele was significantly associated with peripheral edema (OR = 0.32; 95%CI = 0.15–0.68; p = 0.003). Other associations observed were only nominally significant after adjustments: NOS1 rs2682826 A allele and excessive daytime sleepiness and sleep attacks (OR = 1.75; 95%CI = 1.00–3.06, p = 0.048), SOD2 rs4880 T allele and nausea/vomiting (OR = 0.49, 95%CI = 0.25–0.94; p = 0.031), IL1β rs1143623 C allele and orthostatic hypotension (OR = 0.57, 95%CI = 0.32–1.00, p = 0.050), and NOS1 rs2682826 A allele and impulse control disorders (OR = 2.59; 95%CI = 1.09–6.19; p = 0.032). We did not find any associations between selected polymorphisms and motor adverse events. CONCLUSIONS: Apart from some nominally significant associations, one significant association between CAT genetic variability and peripheral edema was observed as well. Therefore, the results of our study suggest some links between genetic variability in inflammation- and oxidative stress-related pathways and non-motor adverse events of dopaminergic treatment. However, the investigated polymorphisms do not play a major role in the occurrence of the disease and the adverse events of dopaminergic treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12974-019-1439-y) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-27 /pmc/articles/PMC6393982/ /pubmed/30813952 http://dx.doi.org/10.1186/s12974-019-1439-y Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Redenšek, Sara
Flisar, Dušan
Kojović, Maja
Kramberger, Milica Gregorič
Georgiev, Dejan
Pirtošek, Zvezdan
Trošt, Maja
Dolžan, Vita
Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease
title Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease
title_full Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease
title_fullStr Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease
title_full_unstemmed Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease
title_short Genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in Parkinson’s disease
title_sort genetic variability of inflammation and oxidative stress genes does not play a major role in the occurrence of adverse events of dopaminergic treatment in parkinson’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393982/
https://www.ncbi.nlm.nih.gov/pubmed/30813952
http://dx.doi.org/10.1186/s12974-019-1439-y
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