Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson's Disease

• Main Authors: Boštjan Petrič (Author), Sara Redenšek Trampuž (Author), Vita Dolžan (Author), Milica Gregorič Kramberger (Author), Maja Trošt (Author), Nikola Maraković (Author), Marko Goličnik (Author), Aljoša Bavec (Author)
• Format: Book
• Published: MDPI AG, 2023-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox12020399; 2076-3921
• Keywords: Parkinson disease; cognitive impairment; paraoxonase 1; paraoxonase activity; single-nucleotide polymorphisms; iFIT; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 12, Iss 2, p 399 (2023)

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 <i>PON1</i>. We found that no genotype or kinetic parameter correlated significantly with cognitive impairment in PD patients. However, we observed associations between <i>PON1</i> rs662 and PON1 K_m (<i>p</i> < 10⁻¹⁰), between <i>PON1</i> rs662 and PON1 V_max (<i>p</i> = 9.33 × 10⁻⁷), and between <i>PON1</i> rs705379 and PON1 V_max (<i>p</i> = 2.21 × 10⁻¹⁰). The present study is novel in three main aspects. (1) It is the first study to investigate associations between the <i>PON1</i> 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.