Abstract
Aims: This study aims to examine the associations between paraoxonase 1 (PON)1 status and acute ischemic stroke (AIS) and consequent disabilities. Methods: This study recruited 122 patients with AIS and 40 healthy controls and assessed the Q192R gene variants, arylesterase (AREase) and chloromethyl phenylacetate (CMPAase) activities, and high-density lipoprotein cholesterol (HDLc) in baseline conditions. AREase and CMPAase were measured 3 months later. The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin score (mRS) were assessed at baseline and 3 and 6 months later. Results: Reduced CMPAase and increased AREase activities are significantly associated with AIS and mRS and NIHSS scores (baseline and 3 and 6 months later). The best predictor of AIS/disabilities was a decrease in the z-unit-based composite zCMPAase-zAREase score. Serum high density lipoprotein cholsterol (HDLc) was significantly correlated with CMPAase, but not AREase, activity and a lowered zCMPAase + zHDLc score was the second best predictor of AIS/disabilities. Regression analysis showed that 34.7% of the variance in baseline NIHSS was explained by zCMPAase-zAREase and zCMPAase + zHDLc composites, HDLc, and hypertension. Neural network analysis showed that stroke was differentiated from controls with an area under the ROC curve of 0.975 using both new composite scores, PON1 status, hypertension, dyslipidemia, previous stroke as body mass index. The PON1 Q192R genotype has many significant direct and mediated effects on AIS/disabilities, however, its overall effect was not significant. Discussion: PON1 status and the CMPAase-HDLc complex play key roles in AIS and its disabilities at baseline and 3 and 6 months later.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The dataset generated during and/or analyzed during the current study will be available from MM upon reasonable request and once the authors have fully exploited the dataset.
References
Abdullah A, Ssefer V, Ertugrul U, Osman E, Esref A, Ugur CM, Adalet A, Yavuz Y, Faysal E, Nebahat T (2013) Evaluation of serum oxidant/antioxidant balance in patients with acute stroke. J Pak Med Assoc 63(5):590–593
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE (1993) 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 24(1):35–41. https://doi.org/10.1161/01.str.24.1.35
Adams HP Jr, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, Woolson RF, Hansen MD (1999) Baseline NIH stroke scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 53(1):126–131. https://doi.org/10.1212/wnl.53.1.126
Alajbegovic A, Djelilovic-Vranic J, Nakicevic A, Todorovic L, Tiric-Campara M (2014) Post stroke depression. Med Arch 68(1):47–50. https://doi.org/10.5455/medarh.2014.68.47-50
Alfieri DF, Lehmann MF, Flauzino T, de Araújo MCM, Pivoto N, Tirolla RM, Simão ANC, Maes M, Reiche EMV (2020) Immune-Inflammatory, metabolic, oxidative, and nitrosative stress biomarkers predict Acute ischemic stroke and short-term outcome. Neurotox Res 38(2):330–343. https://doi.org/10.1007/s12640-020-00221-0
aMaes M (2018) Generalized anxiety disorder (GAD) and Comorbid Major Depression with GAD are characterized by enhanced nitro-oxidative stress, increased lipid peroxidation, and lowered Lipid-Associated antioxidant defenses. Neurotox Res 34(3):489–510. https://doi.org/10.1007/s12640-018-9906-2
aMoreira EG (2019) Why should Psychiatrists and Neuroscientists worry about paraoxonase 1? Curr Neuropharmacol 17(11):1004–1020. https://doi.org/10.2174/1570159X17666181227164947
Banerjee I (2010) Relationship between paraoxonase 1 (PON1) gene polymorphisms and susceptibility of stroke: a meta-analysis. Eur J Epidemiol 25(7):449–458. https://doi.org/10.1007/s10654-010-9470-4
Banks JL, Marotta CA (2007) Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials: a literature review and synthesis. Stroke 38(3):1091–1096. https://doi.org/10.1161/01.STR.0000258355.23810.c6
Benjamin EJ, Virani SS, Callaway CW et al (2018) Heart Disease and Stroke Statistics-2018 update: a Report from the American Heart Association. Circulation 137(12):e67–e492. https://doi.org/10.1161/CIR.0000000000000558
Bhattacharyya T, Nicholls SJ, Topol EJ, Zhang R, Yang X, Schmitt D, Fu X, Shao M, Brennan DM, Ellis SG, Brennan ML, Allayee H, Lusis AJ, Hazen SL (2008) Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. JAMA 299(11):1265–1276. https://doi.org/10.1001/jama.299.11.1265
Bliźniewska-Kowalska K, Gałecki P, Su KP, Halaris A, Szemraj J, Gałecka M (2022) Expression of PON1, PON2, PON3 and MPO genes in patients with depressive Disorders. J Clin Med 11(12):3321. https://doi.org/10.3390/jcm11123321
bMaes M (2018) Early Life Trauma predicts affective phenomenology and the Effects are partly mediated by staging coupled with lowered Lipid-Associated antioxidant defences. Biomol Concepts 9(1):115–130. https://doi.org/10.1515/bmc-2018-0010
bMoreira EG (2019) Lowered PON1 activities are strongly associated with depression and bipolar disorder, recurrence of (hypo)mania and depression, increased disability and lowered quality of life. World J Biol Psychiatry 20(5):368–380. https://doi.org/10.1080/15622975.2017.1322219
Bonita R, Beaglehole R (1988) Recovery of motor function after stroke. Stroke 19(12):1497–1500. https://doi.org/10.1161/01.str.19.12.1497
Brott T, Adams HP Jr, Olinger CP et al (1989) Measurements of acute cerebral infarction: a clinical examination scale. Stroke 20(7):864–870. https://doi.org/10.1161/01.str.20.7.864
Bustamante A, Simats A, Vilar-Bergua A, García-Berrocoso T, Montaner J (2016) Blood/Brain biomarkers of inflammation after Stroke and their Association with Outcome: from C-Reactive protein to Damage-Associated molecular patterns. Neurotherapeutics 13(4):671–684. https://doi.org/10.1007/s13311-016-0470-2
Bustamante A, López-Cancio E, Pich S et al (2017) Blood biomarkers for the early diagnosis of stroke: the stroke-chip study. Stroke 48(9):2419–2425. https://doi.org/10.1161/STROKEAHA.117.017076
Campbell BCV, De Silva DA, Macleod MR, Coutts SB, Schwamm LH, Davis SM, Donnan GA (2019) Ischaemic stroke. Nat Rev Dis Primers 5(1):70. https://doi.org/10.1038/s41572-019-0118-8
Castellazzi M, Trentini A, Romani A, Valacchi G, Bellini T, Bonaccorsi G, Fainardi E, Cavicchio C, Passaro A, Zuliani G, Cervellati C (2016) Decreased arylesterase activity of paraoxonase-1 (PON-1) might be a common denominator of neuroinflammatory and neurodegenerative diseases. Int J Biochem Cell Biol 81(Pt B):356–363. https://doi.org/10.1016/j.biocel.2016.06.008
Ceron JJ, Tecles F, Tvarijonaviciute A (2014) Serum paraoxonase 1 (PON1) measurement: an update. BMC Vet Res 10:74. https://doi.org/10.1186/1746-6148-10-74
Chen H, He Y, Chen S, Qi S, Shen J (2020) Therapeutic targets of oxidative/nitrosative stress and neuroinflammation in ischemic stroke: applications for natural product efficacy with omics and systemic biology. Pharmacol Res 158:104877. https://doi.org/10.1016/j.phrs.2020.104877
Costa LG, Cole TB, Vitalone A, Furlong CE (2005) Measurement of paraoxonase (PON1) status as a potential biomarker of susceptibility to organophosphate toxicity. Clin Chim Acta 352(1–2):37–47. https://doi.org/10.1016/j.cccn.2004.09.019
Dahabreh IJ, Kitsios GD, Kent DM, Trikalinos TA (2010) Paraoxonase 1 polymorphisms and ischemic stroke risk: a systematic review and meta-analysis. Genet Med 12(10):606–615. https://doi.org/10.1097/GIM.0b013e3181ee81c6
Demirdöğen BC, Demirkaya S, Türkanoğlu A, Bek S, Arinç E, Adali O (2009) Analysis of paraoxonase 1 (PON1) genetic polymorphisms and activities as risk factors for ischemic stroke in turkish population. Cell Biochem Funct 27(8):558–567. https://doi.org/10.1002/cbf.1607
Dounousi E, Bouba I, Spoto B, Pappas K, Tripepi G, Georgiou I, Tselepis A, Elisaf M, Tsakiris D, Zoccali C, Siamopoulos K (2016) A Genetic Biomarker of Oxidative Stress, the Paraoxonase-1 Q192R Gene Variant, Associates with Cardiomyopathy in CKD: A Longitudinal Study. Oxid Med Cell Longev 2016:1507270. https://doi.org/10.1155/2016/1507270
Furtado JD, Yamamoto R, Melchior JT, Andraski AB, Gamez-Guerrero M, Mulcahy P, He Z, Cai T, Davidson WS, Sacks FM (2018) Distinct proteomic signatures in 16 HDL (high-Density lipoprotein) subspecies. Arterioscler Thromb Vasc Biol 38(12):2827–2842. https://doi.org/10.1161/ATVBAHA.118.311607
GBD 2016 Neurology Collaborators (2019) Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the global burden of Disease Study 2016. Lancet Neurol 18(5):459–480. https://doi.org/10.1016/S1474-4422(18)30499-X
Geng HH, Wang XW, Fu RL, Jing MJ, Huang LL, Zhang Q, Wang XX, Wang PX (2016) The relationship between C-Reactive protein level and discharge outcome in patients with Acute ischemic stroke. Int J Environ Res Public Health 13(7):636. https://doi.org/10.3390/ijerph13070636
Gorelick PB (2019) The global burden of stroke: persistent and disabling. Lancet Neurol 18(5):417–418. https://doi.org/10.1016/S1474-4422(19)30030-4
Goswami B, Tayal D, Gupta N, Mallika V (2009) Paraoxonase: a multifaceted biomolecule. Clin Chim Acta 410(1–2):1–12. https://doi.org/10.1016/j.cca.2009.09.025
Gupta A, Saluja A, Saraswathy KN, Imnameren L, Yadav S, Dhamija RK (2022) PON1 (paraoxonase 1) Q192R gene polymorphism in ischemic stroke among North Indian Population. Ann Indian Acad Neurol 25(1):100–105. https://doi.org/10.4103/aian.aian_571_21
Heart Association of Thailand. Clinical practice guideline on pharmacological therapy of dyslipidemia for atherosclerotic cardiovascular disease prevention, 2016. Accessed 21-4-2023, http://www.thaiheart.org/Download/2016-RCPT-Dyslipidemia-Guideline.html
Huang Q, Liu YH, Yang QD, Xiao B, Ge L, Zhang N, Xia J, Zhang L, Liu ZJ (2006) Human serum paraoxonase gene polymorphisms, Q192R and L55M, are not associated with the risk of cerebral infarction in chinese Han population. Neurol Res 28(5):549–554. https://doi.org/10.1179/016164106X110337
Johnston KC, Wagner DP, Haley EC Jr, Connors AF Jr, RANTTAS Investigators (2002) Randomized Trial of Tirilazad Mesylate in Acute Stroke. Combined clinical and imaging information as an early stroke outcome measure. Stroke 33(2):466–472. https://doi.org/10.1161/hs0202.102881
Kaypaklı O, Gür M, Harbalıoğlu H, Şeker T, Selek Ş (2016) High morning blood pressure surge is associated with oxidative stress and paraoxonase 1 activity in newly diagnosed hypertensive patients. Clin Exp Hypertens 38(8):680–685. https://doi.org/10.1080/10641963.2016.1200602
Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF (2017) Pathogenic mechanisms following ischemic stroke. Neurol Sci 38(7):1167–1186. https://doi.org/10.1007/s10072-017-2938-1
Kim NS, Kang K, Cha MH, Kang BJ, Moon J, Kang BK, Yu BC, Kim YS, Choi SM, Bang OS (2007) Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans. Biochem Biophys Res Commun 364(1):157–162. https://doi.org/10.1016/j.bbrc.2007.09.119
Kim DS, Burt AA, Ranchalis JE, Richter RJ, Marshall JK, Eintracht JF, Rosenthal EA, Furlong CE, Jarvik GP (2012) Additional common polymorphisms in the PON Gene Cluster Predict PON1 activity but not vascular disease. J Lipids 2012:476316. https://doi.org/10.1155/2012/476316
Koda Y, Tachida H, Soejima M, Takenaka O, Kimura H (2004) Population differences in DNA sequence variation and linkage disequilibrium at the PON1 gene. Ann Hum Genet 68(Pt 2):110–119. https://doi.org/10.1046/j.1529-8817.2003.00077.x
Kotur-Stevuljevic J, Bogavac-Stanojevic N, Jelic-Ivanovic Z, Stefanovic A, Gojkovic T, Joksic J, Sopic M, Gulan B, Janac J, Milosevic S (2015) Oxidative stress and paraoxonase 1 status in acute ischemic stroke patients. Atherosclerosis 241(1):192–198. https://doi.org/10.1016/j.atherosclerosis.2015.05.016
Kulka M (2016) A review of paraoxonase 1 properties and diagnostic applications. Pol J Vet Sci 19(1):225–232. https://doi.org/10.1515/pjvs-2016-0028
Kunutsor SK, Kieneker LM, Bakker SJL, James RW, Dullaart RPF (2017) The inverse association of HDL-cholesterol with future risk of hypertension is not modified by its antioxidant constituent, paraoxonase-1: the PREVEND prospective cohort study. Atherosclerosis 263:219–226. https://doi.org/10.1016/j.atherosclerosis.2017.06.353
Kuriakose D, Xiao Z (2020) Pathophysiology and treatment of stroke: Present Status and Future Perspectives. Int J Mol Sci 21(20):7609. https://doi.org/10.3390/ijms21207609
Laaksonen DE, Niskanen L, Nyyssönen K, Lakka TA, Laukkanen JA, Salonen JT (2008) Dyslipidaemia as a predictor of hypertension in middle-aged men. Eur Heart J 29(20):2561–2568. https://doi.org/10.1093/eurheartj/ehn061
Lehmann ALCF, Alfieri DF, de Araújo MCM et al (2022) Immune-inflammatory, coagulation, adhesion, and imaging biomarkers combined in machine learning models improve the prediction of death 1 year after ischemic stroke. Clin Exp Med 22(1):111–123. https://doi.org/10.1007/s10238-021-00732-w
Li YM, Liu XY (2015) Serum levels of procalcitonin and high sensitivity C-reactive protein are associated with long-term mortality in acute ischemic stroke. J Neurol Sci 352(1–2):68–73. https://doi.org/10.1016/j.jns.2015.03.032
Liu JL, Li JP, Wang XL, Yang Y (2010) Relationship between Q192R polymorphisms in paraoxonase 1 gene and young ischemic stroke. Zhonghua Yi Xue Za Zhi 90(13):912–916
Liu H, Xia P, Liu M, Ji XM, Sun HB, Tao L, Mu QW (2013) PON gene polymorphisms and ischaemic stroke: a systematic review and meta analysis. Int J Stroke 8(2):111–123. https://doi.org/10.1111/j.1747-4949.2012.00813.x
Maes M, Sirivichayakul S, Matsumoto AK, Michelin AP, de Oliveira Semeão L, de Lima Pedrão JV, Moreira EG, Barbosa DS, Carvalho AF, Solmi M, Kanchanatawan B (2020) Lowered antioxidant defenses and increased oxidative toxicity are Hallmarks of Deficit Schizophrenia: a Nomothetic Network Psychiatry Approach. Mol Neurobiol 57(11):4578–4597. https://doi.org/10.1007/s12035-020-02047-5
Maes M, Nikiforov NG, Plaimas K, Suratanee A, Alfieri DF, Vissoci Reiche EM (2021) New drug targets to prevent death due to stroke: a review based on results of protein-protein Interaction Network, Enrichment, and annotation analyses. Int J Mol Sci 22(22):12108. https://doi.org/10.3390/ijms222212108
Maes M, Barbosa DS, Almulla AF, Kanchanatawan B (2022) A novel pathway phenotype of temporal lobe Epilepsy and Comorbid Psychiatric Disorders: results of Precision Nomothetic Medicine. Antioxid (Basel) 11(5):803. https://doi.org/10.3390/antiox11050803
Marchegiani F, Marra M, Olivieri F, Cardelli M, James RW, Boemi M, Franceschi C (2008) Paraoxonase 1: genetics and activities during aging. Rejuvenation Res 11(1):113–127. https://doi.org/10.1089/rej.2007.0582
Marsillach J, Richter RJ, Costa LG, Furlong CE (2021) Paraoxonase-1 (PON1) status analysis using Non-Organophosphate Substrates. Curr Protoc 1(1):e25. https://doi.org/10.1002/cpz1.25
Matsumoto AK, Maes M, Supasitthumrong T, Maes A, Michelin AP, de Oliveira Semeão L, de Lima Pedrão JV, Moreira EG, Kanchanatawan B, Barbosa DS (2021) Deficit schizophrenia and its features are associated with PON1 Q192R genotypes and lowered paraoxonase 1 (PON1) enzymatic activity: effects on bacterial translocation. CNS Spectr 26(4):406–415. https://doi.org/10.1017/S1092852920001388
Matsuo R, Ago T, Hata J, Wakisaka Y, Kuroda J, Kuwashiro T, Kitazono T, Kamouchi M, Fukuoka Stroke Registry Investigators (2016) Plasma C-Reactive protein and clinical outcomes after Acute ischemic stroke: a prospective observational study. PLoS ONE 11(6):e0156790. https://doi.org/10.1371/journal.pone.0156790
Menini T, Gugliucci A (2014) Paraoxonase 1 in neurological disorders. Redox Rep 19(2):49–58. https://doi.org/10.1179/1351000213Y.0000000071
Michelin AP, Maes MHJ, Supasitthumrong T, Limotai C, Matsumoto AK, de Oliveira Semeão L, de Lima Pedrão JV, Moreira EG, Kanchanatawan B, Barbosa DS (2022) Reduced paraoxonase 1 activities may explain the comorbidities between temporal lobe epilepsy and depression, anxiety and psychosis. World J Psychiatry 12(2):308–322. https://doi.org/10.5498/wjp.v12.i2.308
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995) Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 333(24):1581–1587. https://doi.org/10.1056/NEJM199512143332401
Nessler K, Windak A, Grzybczak R, Nessler MB, Siniarski A, Gajos G (2018) High-density lipoprotein (HDL) cholesterol - more complicated than we think? Ann Agric Environ Med 25(3):517–526. https://doi.org/10.26444/aaem/92350
Norrving B, Barrick J, Davalos A (2018) Action Plan for Stroke in Europe 2018–2030. Eur Stroke J 3(4):309–336. https://doi.org/10.1177/2396987318808719
Orellana-Urzúa S, Rojas I, Líbano L, Rodrigo R (2020) Pathophysiology of ischemic stroke: role of oxidative stress. Curr Pharm Des 26(34):4246–4260. https://doi.org/10.2174/1381612826666200708133912
Ozturk U, Ozturk O, Nergiz S, Tamam Y, Varol S (2020) Relationship between Paraoxonase-1 activity and pulse pressure index in patients with a Acute Ischemic Stroke. Dicle Med Journal/Dicle Tip Dergisi 47(4):820–827. https://doi.org/10.5798/dicletip.850304
Park HJ, Kim SK, Park HK, Chung JH (2015) Association between paraoxonase gene polymorphisms and Intracerebral Hemorrhage in a korean Population. J Mol Neurosci 57(3):410–416. https://doi.org/10.1007/s12031-015-0620-8
Phipps MS, Cronin CA (2020) Management of acute ischemic stroke. BMJ 368:l6983. https://doi.org/10.1136/bmj.l6983
Rajkovic MG, Rumora L, Barisic K (2011) The paraoxonase 1, 2 and 3 in humans. Biochem Med (Zagreb 21(2):122–130. https://doi.org/10.11613/bm.2011.020
Richter RJ, Jarvik GP, Furlong CE (2010) Paraoxonase 1 status as a risk factor for disease or exposure. Adv Exp Med Biol 660:29–35. https://doi.org/10.1007/978-1-60761-350-3_4
Shah PK (2010) Evolving concepts on benefits and risks associated with therapeutic strategies to raise HDL. Curr Opin Cardiol 25(6):603–608. https://doi.org/10.1097/HCO.0b013e32833f0382
Shenhar-Tsarfaty S, Waiskopf N, Ofek K, Shopin L, Usher S, Berliner S, Shapira I, Bornstein NM, Ritov Y, Soreq H, Ben Assayag E (2013) Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities. Eur J Neurol 20(6):891–898. https://doi.org/10.1111/ene.12074
Shunmoogam N, Naidoo P, Chilton R (2018) Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance. Vasc Health Risk Manag 14:137–143. https://doi.org/10.2147/VHRM.S165173
Sitia S, Tomasoni L, Atzeni F et al (2010) From endothelial dysfunction to atherosclerosis. Autoimmun Rev 9(12):830–834. https://doi.org/10.1016/j.autrev.2010.07.016
Stinear CM, Lang CE, Zeiler S, Byblow WD (2020) Advances and challenges in stroke rehabilitation. Lancet Neurol 19(4):348–360. https://doi.org/10.1016/S1474-4422(19)30415-6
Tajbakhsh A, Rezaee M, Rivandi M, Forouzanfar F, Afzaljavan F, Pasdar A (2017) Paraoxonase 1 (PON1) and stroke; the dilemma of genetic variation. Clin Biochem 50(18):1298–1305. https://doi.org/10.1016/j.clinbiochem.2017.08.001
Tisato V, Romani A, Tavanti E, Melloni E, Milani D, Bonaccorsi G, Sanz JM, Gemmati D, Passaro A, Cervellati C (2019) Crosstalk between Adipokines and paraoxonase 1: a new potential Axis linking oxidative stress and inflammation. Antioxid (Basel) 8(8):287. https://doi.org/10.3390/antiox8080287
Tohidi M, Hatami M, Hadaegh F, Azizi F (2012) Triglycerides and triglycerides to high-density lipoprotein cholesterol ratio are strong predictors of incident hypertension in Middle Eastern women. J Hum Hypertens 26(9):525–532. https://doi.org/10.1038/jhh.2011.70
Uzun H, Karter Y, Aydin S, Curgunlu A, Simşek G, Yücel R, Vehiyd S, Ertürk N, Kutlu A, Benian A, Yaldiran A, Oztürk E, Erdine S (2004) Oxidative stress in white coat hypertension; role of paraoxonase. J Hum Hypertens 18(7):523–528. https://doi.org/10.1038/sj.jhh.1001697. PMID: 14985779
Varela LM, Meseguer E, Lapergue B, Couret D, Amarenco P, Meilhac O (2020) Changes in high-density lipoproteins related to outcomes in patients with Acute Stroke. J Clin Med 9(7):2269. https://doi.org/10.3390/jcm9072269
Wajngarten M, Silva GS (2019) Hypertension and stroke: update on treatment. Eur Cardiol 14(2):111–115. https://doi.org/10.15420/ecr.2019.11.1
Weimar C, König IR, Kraywinkel K, Ziegler A, Diener HC, German Stroke Study Collaboration (2004) Age and National Institutes of Health Stroke Scale score within 6 hours after onset are accurate predictors of outcome after cerebral ischemia: development and external validation of prognostic models. Stroke 35(1):158–162. https://doi.org/10.1161/01.STR.0000106761.94985.8B
Xiao ZJ, Chen J, Sun Y, Zheng ZJ (2009) Lack of association between the paraoxonase 1 Q/R192 single nucleotide polymorphism and stroke in a chinese cohort. Acta Neurol Belg 109(3):205–209
Xu Y, Wang K, Wang Q, Ma Y, Liu X (2021) The Antioxidant Enzyme PON1: A Potential Prognostic Predictor of Acute Ischemic Stroke. Oxid Med Cell Longev 2021:6677111. https://doi.org/10.1155/2021/6677111
Yildiz A, Gur M, Demirbag R, Yilmaz R, Akyol S, Aslan M, Erel O (2008) Paraoxonase and arylesterase activities in untreated dipper and non-dipper hypertensive patients. Clin Biochem 41(10–11):779–784. https://doi.org/10.1016/j.clinbiochem.2008.02.010
Yıldız M, Çelikel F, Ates O, Taycan SE, Benli I, Demir O (2017) Paraoxonase (PON1) L55M and Q192R polymorphisms in major depression and bipolar affective disorder. Archives of Clinical Psychiatry 44:73–76. https://doi.org/10.1590/0101-60830000000123
Yu H, Huang Y, Chen X, Nie W, Wang Y, Jiao Y, Reed GL, Gu W, Chen H (2017) High-sensitivity C-reactive protein in stroke patients - the importance in consideration of influence of multiple factors in the predictability for disease severity and death. J Clin Neurosci 36:12–19. https://doi.org/10.1016/j.jocn.2016.10.020
Zhang G, Li W, Li Z, Lv H, Ren Y, Ma R, Li X, Kang X, Shi Y, Sun Y (2013) Association between paraoxonase gene and stroke in the Han Chinese population. BMC Med Genet 14:16. https://doi.org/10.1186/1471-2350-14-16
Zhao F, Yue Y, Jiang H, Yuan Y (2019) Shared genetic risk factors for depression and stroke. Prog Neuropsychopharmacol Biol Psychiatry 93:55–70. https://doi.org/10.1016/j.pnpbp.2019.03.003
Zhou Y, Han W, Gong D, Man C, Fan Y (2016) Hs-CRP in stroke: a meta-analysis. Clin Chim Acta 453:21–27. https://doi.org/10.1016/j.cca.2015.11.027
World Stroke Organization Annual Report (2021) Global Stroke Fact Sheet 2019. http://world-stroke.org/news-and-blog/news/wso-annual-report-for-2021. Accessed 26 June 2022
Acknowledgements
Not applicable.
Funding
This research was supported by the Rachadabhisek Research Grant, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. The sponsor had no role in the data or manuscript preparation.
Author information
Authors and Affiliations
Contributions
All authors contributed to the paper. MM and CT designed the study. Statistical analyses were performed by M.M. All authors revised and approved the final draft.
Corresponding author
Ethics declarations
Consent for publication
Not relevant.
Competing Interests
The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported.
Research involving Human Participants and/or Animals
This study was approved by the Institutional Review Board (IRB) of Chulalongkorn University, Bangkok, Thailand (IRB no. 62/073), which complies with the International Guideline for Human Research Protection as required by the Declaration of Helsinki.
Informed consent
Before taking part in the study, all participants and/or their caregivers provided written informed consent.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Brinholi, F.F., Michelin, A.P., Matsumoto, A.K. et al. Paraoxonase 1 status is a major Janus-faced component of mild and moderate acute ischemic stroke and consequent disabilities. Metab Brain Dis 38, 2115–2131 (2023). https://doi.org/10.1007/s11011-023-01232-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11011-023-01232-4