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 Trampuž, Sara (author), Flisar, Dušan (author), Kojović, Maja (author), Gregorič Kramberger, Milica (author), Georgiev, Dejan (author), Pirtošek, Zvezdan (author), Trošt, Maja (author), Dolžan, Vita (author)

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.

• Language: English
• Keywords: Parkinson's disease, susceptibility, polymorphism, inflammation, oxidative stress, adverse events
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2019
• Number of pages: 12 str.
• Numbering: Vol. 16, art. 50
• PID: 20.500.12556/RUL-128757
• UDC: 616.8
• ISSN on article: 1742-2094
• DOI: 10.1186/s12974-019-1439-y
• COBISS.SI-ID: 34211545
• Publication date in RUL: 27.07.2021

Record is a part of a journal

• Title: Journal of neuroinflammation
• Shortened title: J. neuroinflamm.
• Publisher: Springer Nature
• ISSN: 1742-2094
• COBISS.SI-ID: 513966617

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 27.02.2019

Secondary language

• Language: Slovenian
• Keywords: Parkinsonova bolezen, dovzetnost, polimorfizem, vnetje, oksidativni stres, škodljivi dogodki

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0170
• Name: Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

• Funder: ARRS - Slovenian Research Agency
• Funding programme: Grant for young researchers