Investigation of paraoxonase-1 genotype and enzyme-kinetic parameters in the context of cognitive impairment in Parkinson’s disease

Petrič, Boštjan (author), Redenšek Trampuž, Sara (author), Dolžan, Vita (author), Gregorič Kramberger, Milica (author), Trošt, Maja (author), Maraković, Nikola (author), Goličnik, Marko (author), Bavec, Aljoša (author)

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 K$_m$ and V$_{max}$ 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 K$_m$ (p < 10$^{−10}$), between PON1 rs662 and PON1 V$_{max}$ (p = 9.33 × 10$^{−7}$), and between PON1 rs705379 and PON1 V$_{max}$ (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 K$_m$ and V$_{max}$ 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.

• Language: English
• Keywords: Parkinson disease, cognitive impairment, paraoxonase 1, paraoxonase activity, single-nucleotide polymorphisms, iFIT
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 16 str.
• Numbering: Vol. 12, iss. 2, art. 399
• PID: 20.500.12556/RUL-154047
• UDC: 616.8
• ISSN on article: 2076-3921
• DOI: 10.3390/antiox12020399
• COBISS.SI-ID: 141510403
• Publication date in RUL: 22.01.2024

Record is a part of a journal

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

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

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
• Project number: J7-2600
• Name: Presnovne možganske spremembe nevrodegenerativnih demenc in njihove korelacije s histopatološkimi spremembami v možganih