Document Type : Original Article
Authors
- Mohammad Reza Jahed 1
- Seyed Amir Hassan Habibi 2
- Golnaz Vaseghi 3
- Hasan Amiri 4
- Hamed Montazeri 5
- Azadeh Eshraghi 1
1 Department of Clinical Pharmacy, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
2 Department of Neurology, Movement Disorders Clinic, Rasool Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
3 Isfahan Cardiovascular Research Center, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Emergency Medicine, School of Medicine, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran Emergency Medicine Management Research Center, Iran University of Medical Sciences, Tehran, Iran
5 Department of Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
Abstract
Background: Up to know, limited and contradictory results have been published about the role of prognostic values of lipid profile and proprotein convertase subtilisin/kexin type 9 (PCSK9) in Parkinson’s disease (PD). The aim of the present study is to investigate the role of lipid profile and PCSK9 in patients with PD and compare it with healthy individuals.
Methods: In this case-control study, 31 individuals diagnosed with PD were compared with 31 healthy individuals. The lipid profile and PCSK9 of research participants were measured and the resulting data were analyzed using SPSS software. The P-values smaller than 0.05 were considered significant.
Results: The mean age of participants in the PD and control group was 56.9 ± 8.8 and 53.7 ± 10.1 years, respectively (P > 0.050). 27 individuals (87.1%) in the PD group and 13 individuals (41.9%) in the control group were men. Low-density lipoprotein (LDL) level (84.2 ± 24.9 ml/dl vs. 105.5 ± 16.8, P < 0.001), high-density lipoprotein (HDL) level (45.5 ± 8.7 ml/dl vs. 51.1 ± 9.5 ml/dl, P < 0.001), and total cholesterol (155.3 ± 31.2 ml/dl vs. 192.8 ± 32.5 ml/dl, P < 0.001) were lower and triglyceride (TG) level was higher in the PD group (133.3 ± 79.3 ml/dl vs. 131.2 ± 58.6 ml/dl, P = 0.900) compared with the control group. PCSK9 level was higher in the PD group, but no significant difference was found (141.6 ± 70.0 vs. 129.7 ± 51.0 ng/ml, P = 0.500) compared to healthy subjects. Moreover, there was no relation between PCSK9 and severity of PD.
Conclusion: Our findings showed that individuals with PD had lower levels of HDL, LDL, and total cholesterol compared with the control group. However, higher concentrations of PCSK9 were observed in patients with PD compared with healthy volunteers.
Keywords
- Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: A review. JAMA 2014; 311(16): 1670-83.
- Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson's disease: A systematic review and meta-analysis. Mov Disord 2014; 29(13): 1583-90.
- Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: A meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007; 370(9602): 1829-39.
- Liu JP, Tang Y, Zhou S, Toh BH, McLean C, Li H. Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Mol Cell Neurosci 2010; 43(1): 33-42.
- Vance JE. Dysregulation of cholesterol balance in the brain: Contribution to neurodegenerative diseases. Dis Model Mech 2012; 5(6): 746-55.
- Huang X, Chen H, Miller WC, Mailman RB, Woodard JL, Chen PC, et al. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease. Mov Disord 2007; 22(3): 377-81.
- de Lau LM, Koudstaal PJ, Hofman A, Breteler MM. Serum cholesterol levels and the risk of Parkinson's disease. Am J Epidemiol 2006; 164(10): 998-1002.
- Hu G. Total cholesterol and the risk of Parkinson's disease: A review for some new findings. Parkinson's Dis 2010; 2010: 836962.
- Wahner AD, Bronstein JM, Bordelon YM, Ritz B. Statin use and the risk of Parkinson disease. Neurology 2008; 70(16 Pt 2): 1418-22.
- Gao X, Simon KC, Schwarzschild MA, Ascherio A. Prospective study of statin use and risk of Parkinson disease. Arch Neurol 2012; 69(3): 380-4.
- Bykov K, Yoshida K, Weisskopf MG, Gagne JJ. Confounding of the association between statins and Parkinson disease: Systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2017; 26(3): 294-300.
- Maxwell KN, Breslow JL. Adenoviral-mediated expression of Pcsk9 in mice results in a low-density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci USA 2004; 101(18): 7100-5.
- Poirier S, Mayer G. The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol. Drug Des Devel Ther 2013; 7: 1135-48.
- Careskey HE, Davis RA, Alborn WE, Troutt JS, Cao G, Konrad RJ. Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res 2008; 49(2): 394-8.
- Welder G, Zineh I, Pacanowski MA, Troutt JS, Cao G, Konrad RJ. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res 2010; 51(9): 2714-21.
- Awan Z, Seidah NG, MacFadyen JG, Benjannet S, Chasman DI, Ridker PM, et al. Rosuvastatin, proprotein convertase subtilisin/kexin type 9 concentrations, and LDL cholesterol response: The JUPITER trial. Clin Chem 2012; 58(1): 183-9.
- Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, et al. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc Natl Acad Sci U S A 2003; 100(21): 12027-32.
- Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice. J Lipid Res 2003; 44(11): 2109-19.
- Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci U S A 2005; 102(15): 5374-9.
- Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 2003; 34(2): 154-6.
- Guo YL, Liu J, Xu RX, Zhu CG, Wu NQ, Jiang LX, et al. Short-term impact of low-dose atorvastatin on serum proprotein convertase subtilisin/kexin type 9. Clin Drug Investig 2013; 33(12): 877-83.
- Khera AV, Qamar A, Reilly MP, Dunbar RL, Rader DJ. Effects of niacin, statin, and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 levels in patients with dyslipidemia. Am J Cardiol 2015; 115(2): 178-82.
- Wu Q, Tang ZH, Peng J, Liao L, Pan LH, Wu CY, et al. The dual behavior of PCSK9 in the regulation of apoptosis is crucial in Alzheimer's disease progression (Review). Biomed Rep 2014; 2(2): 167-71.
- Zhao XS, Wu Q, Peng J, Pan LH, Ren Z, Liu HT, et al. Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression. Mol Med Rep 2017; 15(2): 712-8.
- Benn M, Nordestgaard BG, Frikke-Schmidt R, Tybjaerg -Hansen A. Low PCSK9 and LDL cholesterol and risk of dementia, Parkinson's disease, and epilepsy - a Mendelian randomization study. Circulation 2015; 132(suppl_3): A19109.
- Victor RG, Haley RW, Willett DL, Peshock RM, Vaeth PC, Leonard D, et al. The Dallas Heart Study: A population-based probability sample for the multidisciplinary study of ethnic differences in cardiovascular health. Am J Cardiol 2004; 93(12): 1473-80.
- Taylor Tavares AL, Jefferis GS, Koop M, Hill BC, Hastie T, Heit G, et al. Quantitative measurements of alternating finger tapping in Parkinson's disease correlate with UPDRS motor disability and reveal the improvement in fine motor control from medication and deep brain stimulation. Mov Disord 2005; 20(10): 1286-98.
- Pedersen KF, Larsen JP, Aarsland D. Validation of the Unified Parkinson's Disease Rating Scale (UPDRS) section I as a screening and diagnostic instrument for apathy in patients with Parkinson's disease. Parkinsonism Relat Disord 2008; 14(3): 183-6.
- Guo X, Song W, Chen K, Chen X, Zheng Z, Cao B, et al. The serum lipid profile of Parkinson's disease patients: A study from China. Int J Neurosci 2015; 125(11): 838-44.
- Huang X, Abbott RD, Petrovitch H, Mailman RB, Ross GW. Low LDL cholesterol and increased risk of Parkinson's disease: Prospective results from Honolulu-Asia Aging Study. Mov Disord 2008; 23(7): 1013-8.
- Ikeda K, Nakamura Y, Kiyozuka T, Aoyagi J, Hirayama T, Nagata R, et al. Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson's disease: Changes linked to disease progression. Neurodegener Dis 2011; 8(4): 252-8.
- Hu G, Antikainen R, Jousilahti P, Kivipelto M, Tuomilehto J. Total cholesterol and the risk of Parkinson disease. Neurology 2008; 70(21): 1972-9.
- Simon KC, Chen H, Schwarzschild M, Ascherio A. Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease. Neurology 2007; 69(17): 1688-95.
- Miyake Y, Tanaka K, Fukushima W, Sasaki S, Kiyohara C, Tsuboi Y, et al. Case-control study of risk of Parkinson's disease in relation to hypertension, hypercholesterolemia, and diabetes in Japan. J Neurol Sci 2010; 293(1-2): 82-6.
- Nassoury N, Blasiole DA, Tebon OA, Benjannet S, Hamelin J, Poupon V, et al. The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR. Traffic 2007; 8(6): 718-32.
- Homer VM, Marais AD, Charlton F, Laurie AD, Hurndell N, Scott R, et al. Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa. Atherosclerosis 2008; 196(2): 659-66.
- Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation. Proc Natl Acad Sci USA 2003; 100(3): 928-33.