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Licensed Unlicensed Requires Authentication Published by De Gruyter January 23, 2016

Paraoxonase 1 activity and polymorphisms in multiple sclerosis patients

Monika Ď Ďurfinová, Radka Bartová, Ľubica Procházková, Darina Petrleničová, Pavel Sýkora and Vanda Repiská
From the journal Biologia


The pathophysiology of multiple sclerosis (MS) includes also the vascular abnormalities. Recent reports on changes in venous cerebrospinal outflow and the investigation of immunomodulatory properties of several vascular mediators on the molecular level have added new information to hypotheses on vascular pathology as determining factor in the pathophysiology of MS. We assessed changes in serum paraoxonase 1 (PON1) activities in MS patients and polymorphism of PON1 as a risk factor for MS. The main role of serum PON1 is hydrolysis of lipid peroxides and protection of lowdensity lipoprotein particles from oxidation. These events could play a role in lowering the risk of atherogenesis and vascular complications development in MS. There are controversial results about association of two main polymorphisms in paraoxonase coding region (PON1 55L/M, PON1 192Q/R) and risk of MS in different populations. Our results support studies that PON1 polymorphisms are probably not a risk factor of MS development.


Allen N.B., Lichtman J.H., Cohen H.W., Fang J., Brass L.M. & Alderman M.H. 2008. Vascular disease among hospitalized multiple sclerosis patients. Neuroepidemiology 30: 234-238.10.1159/000128103Search in Google Scholar

Aviram M., Rosenblat M., Billecke S., Erogul J., Sorenson R. & Bisgaier C.L. 1999. Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radical Biol. Med. 26: 892-904.10.1016/S0891-5849(98)00272-XSearch in Google Scholar

Bassett C.N. & Montine T.J. 2003. Lipoproteins and lipid peroxidation in Alzheimer’s disease. J. Nutr. Health Aging 7: 24-29.Search in Google Scholar

Diekstra F.P., Beleza-Meireles A., Leigh N.P., Shaw C.E. & Al- Chalabi A. 2009. Interaction between PON1 and population density in amyotrophic lateral sclerosis. Neuroreport 20: 186-190.10.1097/WNR.0b013e32831af220Search in Google Scholar

Draganov D.I. & La Du B.N. 2004. Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch. Pharmacol. 369: 78-88.10.1007/s00210-003-0833-1Search in Google Scholar

Duric G., Svetel M., Nikolaevic S.I., Dragadevic N., Gavrilovic J. & Kostic V.S. 2007. Polymorphism in the genes of cytochrome oxidase P450 2D6 (CYP2D6), paraoxonase 1 (PON1) and apolipoprotein E (APOE) as risk factors for Parkinson’s disease. Vojnosanitetski Pregled 64: 25-30.Search in Google Scholar

Ferretti G., Bacchetti T., Principi F., Di Ludovico F., Viti B., Angeleri V.A., Danni M. & Provinciali L. 2005. Increased levels of lipid hydroperoxides in plasma of patients with multiple sclerosis: a relationship with paraoxonase activity. Mult. Scler. 11: 677-682.10.1191/1352458505ms1240oaSearch in Google Scholar

Hadjigeorgiou G.M., Malizos K., Dardiotis E., Aggelakis K., Dardioti M., Zibis A., Dimitroulias A., Scarmeas N., Tsezou A. & Karantanas A. 2007. Paraoxonase 1 gene polymorphisms in patients with osteonecrosis of the femoral head with and without cerebral white matter lesions. J. Orthop. Res. 25: 1087-1093.10.1002/jor.20393Search in Google Scholar

Humbert R., Adler D.A., Disteche C.M., Hassett C., Omiecinski C.J. & Furlong C.E. 1993. The molecular-basis of the human serum paraoxonase activity polymorphism. Nat. Genet. 3: 73-76.10.1038/ng0193-73Search in Google Scholar

Christiansen C.F., Christiansen S., Farkas D.K., Miret M., Sorensen H.T. & Pedersen L. 2010. Risk of arterial cardiovascular diseases in patients with multiple sclerosis: a population-based cohort study. Neuroepidemiology 35: 267-274.10.1159/000320245Search in Google Scholar

Imai Y., Morita H., Kurihara H., Sugiyama T., Kato N., Ebihara A., Hamada C., Kurihara Y., Shindo T., Oh-Hashi Y. & Yazaki Y. 2000. Evidence for association between paraoxonase gene polymorphism and atherosclerotic diseases. Atherosclerosis 149: 435-442.10.1016/S0021-9150(99)00340-8Search in Google Scholar

Inglese M., Park S.J., Johnson G., Babb J.S., Miles L., Jaggi H., Herbert J. & Grossman R.I. 2007. Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T. Arch. Neurol. 64: 196-202.10.1001/archneur.64.2.196Search in Google Scholar PubMed

Jamroz-Wisniewska A., Beltowski J., Stelmasiak Z. & Bartosik- Psujek H. 2009. Paraoxonase 1 activity in different types of multiple sclerosis. Mult. Scler. 15: 399-402.10.1177/1352458508098371Search in Google Scholar

Law M., Saindane A.M., Ge Y., Babb J.S., Johnson G., Mannon L.J., Herbert J. & Grossman R.I. 2004. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology 231: 645-652.10.1148/radiol.2313030996Search in Google Scholar

Levine S.M. 1992. The role of reactive oxygen species in the pathogenesis of multiple sclerosis. Med. Hypotheses 39: 271-274.10.1016/0306-9877(92)90121-RSearch in Google Scholar

Martinez C., García-Martin E., Benito-León J., Calleja P., Díaz- Sanchez M., Pisa D., Alonso-Navarro H., Ayuso-Peralta L., Torrecilla D., Agúndez J.A.G. & Jiménez-Jiménez F.J. 2010. Paraoxonase 1 polymorphisms are not related with the risk for multiple sclerosis. Neuromol. Med. 12: 217-223.10.1007/s12017-009-8095-9Search in Google Scholar PubMed

Moghtaderi A., Hashemi M., Sharafaddinzadeh N., Dabiri S., Moazeni-Roodi A., Ramroodi N. & Zolfaghari M. 2011. Lack of association between paraoxonase 1 Q192R polymorphism and multiple sclerosis in relapse phase: a case-control study. Clin. Biochem. 44: 795-798.10.1016/j.clinbiochem.2011.04.010Search in Google Scholar PubMed

Polman C.H., Reingold S.C., Banwell B., Clanet M., Cohen J.A., Filippi M., Fujihara K., Havrdova E., Hutchinson M., Kappos L., Lublin F.D., Montalban X., O’Connor P., Sandberg- Wollheim M., Thompson A.J., Waubant E., Weinshenker B. & Wolinsky J.S. 2011. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 69: 292-302.10.1002/ana.22366Search in Google Scholar PubMed PubMed Central

Shin B.S., Oh S.Y., Kim Y.S. & Kim K.W. 2008. The paraoxonase gene polymorphism in stroke patients and lipid profile. Acta Neurol. Scand. 117: 237-243.10.1111/j.1600-0404.2007.00929.xSearch in Google Scholar PubMed

Sidoti A., Antognelli C., Rinaldi C., D’Angelo R., Dattola V., Girlanda P., Talesa V. & Amato A. 2007. Glyoxalase I A111E, paraoxonase 1 Q192R and L55M polymorphisms: susceptibility factors of multiple sclerosis? Mult. Scler. 13: 446-453.Search in Google Scholar

Sýkora P., Repiská V. & Halčák L. 2010. Establishment of paraoxonase and arylesterase activity of paraoxonase 1 (PON1) in dependence on 55(L/M) and 192(Q/R) DNA polymorphism in adult people with Down syndrome. Journal of Special Education and Rehabilitation 11: 103-113.Search in Google Scholar

Zamboni P., Galeotti R., Menegatti E., Malagoni A.M., Tacconi G., Dall’Ara S., Bartolomei I. & Salvi F. 2009. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 80: 392-399. 10.1136/jnnp.2008.157164Search in Google Scholar PubMed PubMed Central

Received: 2015-10-20
Accepted: 2015-12-10
Published Online: 2016-1-23
Published in Print: 2015-12-1

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