Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. DNA Isolation and Genotyping
2.3. Enzyme-Kinetic Measurements
2.4. Statistical Analysis
3. Results
3.1. General Characteristics of the Study Population
3.2. Association between Genotype and Kinetic Parameters
3.3. Association between Genetic, Enzyme-Kinetic, and Clinical Parameters
4. Discussion
4.1. Methodological Improvements
4.2. Associations between PON1 Genotypes and Kinetic Parameters
4.3. Associations between Genetic, Enzyme-Kinetic, and Clinical Parameters
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | All Patients (N = 231) | Patients with Defined Dementia Status (N = 207) | |
---|---|---|---|
Gender | Male (%) | 132 (57.1) | 118 (57.0) |
Female (%) | 99 (42.9) | 89 (43.0) | |
Age at inclusion into the study | Median (25–75%), years | 72.3 (65.5–78.0) | 72.8 (65.9–78.2) |
Dementia | Yes (%) | 89 (38.5) | 89 (43.0) |
No (%) | 118 (51.1) | 118 (57.0) | |
MMSE score | Median (25–75%) | 27 (24–29) | 27 (24–29) |
PON1 Km for DHC | Median (25–75%) [μM] | 5.9 (4.9–6.9) * | 5.9 (4.9–7.1) ** |
PON1 Vmax for DHC | Median (25–75%) [μM/min] | 81.5 (67.1–99.9) *** | 79.2 (62.2–99.8) **** |
rs854560 | p-Value | ||||
---|---|---|---|---|---|
Genotype | TT (MM) | TA (LM) | AA (LL) | ||
rs662 | AA (QQ) | N = 25 Km = 6.74 (5.85–7.55) | N = 54 Km = 6.45 (5.92–7.70) | N = 34 Km = 6.75 (5.98–7.95) | 0.614 |
GA (QR) | N = 0 | N = 48 Km = 5.27 (4.34–5.53) | N = 39 Km = 5.12 (4.57–5.77) | 0.556 | |
GG (RR) | N = 0 | N = 0 | N = 14 Km = 3.54 (2.91–4.03) | ||
p-value | 2.53 × 10−8 | 3.44 × 10−10 |
rs705381 | p-Value | ||||
---|---|---|---|---|---|
Genotype | TT | TC | CC | ||
rs705379 | AA | N = 0 | N = 0 | N = 42 Vmax = 66.00 (54.74–77.53) | |
GA | N = 0 | N = 29 Vmax = 83.94 (69.80–98.85) | N = 48 Vmax = 80.08 (68.15–99.01) | 0.697 | |
GG | N = 14 Vmax = 114.53 (79.62–139.50) | N = 24 Vmax = 90.13 (74.36–141.98) | N = 20 Vmax = 99.31 (91.29–114.53) | 0.612 | |
p-value | 0.148 | 5.14 × 10−7 |
rs854560 | p-Value | ||||
---|---|---|---|---|---|
Genotype | TT (MM) | TA (LM) | AA (LL) | ||
rs705379 | AA | N = 15 Vmax = 70.16 (56.41–81.70) | N = 20 Vmax = 66.00 (53.16–77.00) | N = 7 Vmax = 64.77 (48.59–70.95) | 0.568 |
GA | N = 3 Vmax = 71.29 (71.18–79.64) | N = 48 Vmax = 79.12 (65.80–96.52) | N = 26 Vmax = 91.79 (73.30–103.80) | 0.136 | |
GG | N = 0 | N = 19 Vmax = 97.41 (88.09–110.79) | N = 39 Vmax = 99.45 (77.24–138.70) | 0.697 | |
p-value | 0.36 | 1.3 × 10−5 | 0.006 |
Comparison | Homozygote 1 | Heterozygote | Homozygote 2 | p-Value |
---|---|---|---|---|
rs662 and Vmax | AA (QQ) 91.86 (71.62–111.92) N = 93 | GA (QR) 77.44 (64.89–94.32) N = 72 | GG (RR) 59.13 (42.26–73.19) N = 12 | 9.33 × 10−7 |
rs662 and Km | AA (QQ) 6.59 (5.94–7.74) N = 113 | GA (QR) 5.19 (4.51–5.73) N = 87 | GG (RR) 3.54 (2.91–4.02) N = 14 | <10−10 |
rs705379 and Vmax | AA 66.00 (54.96–77.42) N = 42 | GA 81.62 (70.21–98.54) N = 77 | GG 99.45 (77.24–138.70) N = 58 | 2.21 × 10−10 |
SNP | Genotype | OR | Dementia N (%) | Without Dementia N (%) | 95% CI | p-Value |
---|---|---|---|---|---|---|
rs662 | AA | Ref. | 47 (43.9) | 60 (56.1) | ||
GA | 0.801 | 32 (38.6) | 51 (61.2) | 0.447–1.436 | 0.457 | |
GG | 1.824 | 10 (58.8) | 7 (41.2) | 0.646–5.152 | 0.257 | |
rs854560 | TT | Ref. | 12 (44.4) | 15 (55.6) | ||
TA | 0.991 | 42 (44.2) | 53 (55.8) | 0.419–2.342 | 0.983 | |
AA | 0.365 | 35 (41.2) | 50 (58.8) | 0.365–2.096 | 0.764 | |
rs705379 | AA | Ref. | 21 (39.6) | 32 (60.4) | ||
GA | 1.195 | 40 (44.0) | 51 (56.0) | 0.600–2.380 | 0.612 | |
GG | 1.219 | 28/44.4) | 35 (55.6) | 0.581–2.559 | 0.601 | |
rs705381 | TT | Ref. | 9 (56.3) | 7 (43.7) | ||
TC | 0.660 | 28 (45.9) | 33 (54.1) | 0.218–2.000 | 0.463 | |
CC | 0.519 | 52 (40.0) | 78 (60.0) | 0.182–1.479 | 0.219 |
MMSE Score (p-Value, Correlation Coefficient, N) | Presence of Dementia (p-Value, N) | |
---|---|---|
Km | p = 0.387, CC = −0.073, N = 126 | p = 0.073, N = 194 |
Vmax | p = 0.328, CC = 0.091, N = 103 | p = 0.138, N = 159 |
rs662 | p = 0.046, N = 137 | p = 0.295, N = 207 |
rs854560 | p = 0.762, N = 137 | p = 0.907, N = 207 |
rs705379 | p = 0.863, N = 137 | p = 0.846, N = 207 |
rs705381 | p = 0.326, N = 137 | p = 0.400, N = 207 |
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Petrič, B.; Redenšek Trampuž, S.; Dolžan, V.; Gregorič Kramberger, M.; Trošt, M.; Maraković, N.; Goličnik, M.; Bavec, A. Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson’s Disease. Antioxidants 2023, 12, 399. https://doi.org/10.3390/antiox12020399
Petrič B, Redenšek Trampuž S, Dolžan V, Gregorič Kramberger M, Trošt M, Maraković N, Goličnik M, Bavec A. Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson’s Disease. Antioxidants. 2023; 12(2):399. https://doi.org/10.3390/antiox12020399
Chicago/Turabian StylePetrič, Boštjan, Sara Redenšek Trampuž, Vita Dolžan, Milica Gregorič Kramberger, Maja Trošt, Nikola Maraković, Marko Goličnik, and Aljoša Bavec. 2023. "Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson’s Disease" Antioxidants 12, no. 2: 399. https://doi.org/10.3390/antiox12020399
APA StylePetrič, B., Redenšek Trampuž, S., Dolžan, V., Gregorič Kramberger, M., Trošt, M., Maraković, N., Goličnik, M., & Bavec, A. (2023). Investigation of Paraoxonase-1 Genotype and Enzyme-Kinetic Parameters in the Context of Cognitive Impairment in Parkinson’s Disease. Antioxidants, 12(2), 399. https://doi.org/10.3390/antiox12020399