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Title:Investigation of paraoxonase-1 genotype and enzyme-kinetic parameters in the context of cognitive impairment in Parkinson’s disease
Authors:ID Petrič, Boštjan (Author)
ID Redenšek Trampuž, Sara (Author)
ID Dolžan, Vita (Author)
ID Gregorič Kramberger, Milica (Author)
ID Trošt, Maja (Author)
ID Maraković, Nikola (Author)
ID Goličnik, Marko (Author)
ID Bavec, Aljoša (Author)
Files:.pdf PDF - Presentation file, download (1,14 MB)
MD5: 45C1E6CCE7C962A97D878B5063419FCC
 
URL URL - Source URL, visit https://www.mdpi.com/2076-3921/12/2/399
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo UKC LJ - Ljubljana University Medical Centre
Abstract:Cognitive impairment is a common non-motor symptom of Parkinson’s disease (PD), which often progresses to PD dementia. PD patients with and without dementia may differ in certain biochemical parameters, which could thus be used as biomarkers for PD dementia. The enzyme paraoxonase 1 (PON1) has previously been investigated as a potential biomarker in the context of other types of dementia. In a cohort of PD patients, we compared a group of 89 patients with cognitive impairment with a group of 118 patients with normal cognition. We determined the kinetic parameters Km and Vmax for PON1 for the reaction with dihydrocoumarin and the genotype of four single nucleotide polymorphisms in PON1. We found that no genotype or kinetic parameter correlated significantly with cognitive impairment in PD patients. However, we observed associations between PON1 rs662 and PON1 Km (p < 10−10), between PON1 rs662 and PON1 Vmax (p = 9.33 × 10−7), and between PON1 rs705379 and PON1 Vmax (p = 2.21 × 10−10). The present study is novel in three main aspects. (1) It is the first study to investigate associations between the PON1 genotype and enzyme kinetics in a large number of subjects. (2) It is the first study to report kinetic parameters of PON1 in a large number of subjects and to use time-concentration progress curves instead of initial velocities to determine Km and Vmax in a clinical context. (3) It is also the first study to calculate enzyme-kinetic parameters in a clinical context with a new algorithm for data point removal from progress curves, dubbed iFIT. Although our results suggest that in the context of PD, there is no clinically useful correlation between cognitive status on the one hand and PON1 genetic and enzyme-kinetic parameters on the other hand, this should not discourage future investigation into PON1’s potential associations with other types of dementia.
Keywords:Parkinson disease, cognitive impairment, paraoxonase 1
Publication status:Published
Publication version:Version of Record
Year of publishing:2023
Number of pages:str. 1-16
Numbering:Vol. 12, iss. 2
PID:20.500.12556/DiRROS-31482 New window
UDC:616.8
ISSN on article:2076-3921
DOI:10.3390/antiox12020399 New window
COBISS.SI-ID:141510403 New window
Note: Nasl. z nasl. zaslona; Opis z dne 13. 2. 2023;
Publication date in DiRROS:03.08.2026
Views:162
Downloads:102
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Record is a part of a journal

Title:Antioxidants
Shortened title:Antioxidants
Publisher:MDPI AG
ISSN:2076-3921
COBISS.SI-ID:522976025 New window

Document is financed by a project

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:P1-0170-2018
Name:Molekulski mehanizmi uravnavanja celičnih procesov v povezavi z nekaterimi boleznimi pri človeku

Funder:ARIS - Slovenian Research and Innovation Agency
Project number:J7-2600-2020
Name:Presnovne možganske spremembe nevrodegenerativnih demenc in njihove korelacije s histopatološkimi spremembami v možganih

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.

Secondary language

Language:Slovenian
Keywords:Parkinsonova bolezen, kognitivne motnje, paraoksonaza 1


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