Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

1.
Li HL, Liu DP, Liang CC: Paraoxonase gene polymorphisms, oxidative stress, and diseases. J Mol Med 2003;81:766–779.
2.
Ng CJ, Shih DM, Hama SY, Villa N, Navab M, Reddy ST: The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 2005;38:153–163.
3.
Ng CJ, Wadleigh DJ, Gangopadhyay A, Hama S, Grijalva VR, Navab M, Fogelman AM, Reddy ST: Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 2001;276:44444–44449.
4.
Martinelli N, Girelli D, Olivieri O, Stranieri C, Trabetti E, Pizzolo F, Friso S, Tenuti I, Cheng S, Grow MA, Pignatti PF, Corrocher R: Interaction between smoking and PON2 Ser311Cys polymorphism as a determinant of the risk of myocardial infarction. Eur J Clin Invest 2004;34:14–20.
5.
Mashima R, Witting PK, Stocker R: Oxidants and antioxidants in atherosclerosis. Curr Opin Lipidol 2001;12:411–418.
6.
Imai Y, Morita H, Kurihara H, Sugiyama T, Kato N, Ebihara A, Hamada C, Kurihara Y, Shindo T, Oh-hashi Y, Yazaki Y: Evidence for association between paraoxonase gene polymorphisms and atherosclerotic disease. Atherosclerosis 2000;149:435–442.
7.
Baum L, Ng HK, Woo KS, Tomlinson B, Rainer TH, Chen X, Cheung WS, Chan DK, Thomas GN, Tong CS, Wong KS: Paraoxonase 1 gene Q192R polymorphism affects stroke and myocardial infarction risk. Clin Biochem 2006;39:191–195.
8.
Ueno T, Shimazaki E, Matsumoto T, Watanabe H, Tsunemi A, Takahashi Y, Mori M, Hamano R, Fujioka T, Soma M, Matsumoto K, Konmatsuse K: Paraoxonase1 polymorphism Leu-Met55 is associated with cerebral infarction in Japanese population. Med Sci Monit 2003;9:CR208–212.
9.
Ranade K, Kirchgessner TG, Iakoubova OA, Devlin JJ, Del Monte T, Vishnupad P, Hui L, Tsuchihashi Z, Sacks FM, Sabatine MS, Braunwald E, White TJ, Shaw PM, Dracopoli NC: Evaluation of the paraoxonases as candidate genes for stroke: Gln192Arg polymorphism in the paraoxonase 1 gene is associated with increased risk of stroke. Stroke 2005;36:2346–2350.
10.
Voetsch B, Benke KS, Damasceno BP, Siqueira LH, Loscalzo J: Paraoxonase 192 Gln→Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults. Stroke 2002;33:1459–1464.
11.
Topic E, Timundic AM, Ttefanovic M, Demarin V, Vukovic V, Lovrencic-Huzjan A, Zuntar I: Polymorphism of apoprotein E (APOE), methylenetetrahydrofolate reductase (MTHFR) and paraoxonase (PON1) genes in patients with cerebrovascular disease. Clin Chem Lab Med 2001;39:346–350.
12.
Pasdar A, Ross-Adams H, Cumming A, Cheung J, Whalley L, St Clair D, MacLeod MJ: Paraoxonase gene polymorphisms and haplotype analysis in a stroke population. BMC Med Genet 2006;7:28.
13.
Wang XY, Xue YM, Wen SJ, Zhang NL, Ji Z, Pan SY: The association of paraoxonase 2 gene C311S variant with ischemic stroke in Chinese type 2 diabetes mellitus patients. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003;20:215–219.
14.
Deakin SP, James RW: Genetics and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 2004;107:435–447.
15.
Hatano S: Experience from a multicentre stroke register: a preliminary report. Bull World Health Organ 1976;54:541–553.
16.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 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 1993;24:35–41.
17.
Alberti KG, Zimmet PZ: Definition, diagnosis, and classification of diabetes mellitus: provisional report of a WHO consultation. Diabet Med 1998;15:539–553.
18.
Mackness B, Durrington PN, Abuashia B, Boulton AJ, Mackness MI: Low paraoxonase activity in type II diabetes mellitus complicated by retinopathy. Clin Sci (Lond) 2000;98:355–363.
19.
Drouet L: Atherothrombosis as a systemic disease. Cerebrovasc Dis 2002;13(suppl 1):1–6.
20.
Stevens VL, Rodriguez C, Pavluck AL, Thun MJ, Calle EE: Association of polymorphisms in the paraoxonase 1 gene with breast cancer incidence in the CPS-II Nutrition Cohort. Cancer Epidemiol Biomarkers Prev 2006;15:1226–1228.
21.
Antognelli C, Mearini L, Talesa VN, Giannantoni A, Mearini E: Association of CYP17, GSTP1, and PON1 polymorphisms with the risk of prostate cancer. Prostate 2005;63:240–251.
22.
Slowik A, Tomik B, Wolkow PP, Partyka D, Turaj W, Malecki MT, Pera J, Dziedzic T, Szczudlik A, Figlewicz DA: Paraoxonase gene polymorphisms and sporadic ALS. Neurology, 2006;67:766–770.
23.
Erlich PM, Lunetta KL, Cupples LA, Huyck M, Green RC, Baldwin CT, Farrer LA; MIRAGE Study Group: Polymorphisms in the PON gene cluster are associated with Alzheimer disease. Hum Mol Genet 2006;15:77–85.
24.
Rosenblat M, Hayek T, Hussein K, Aviram M: Decreased macrophage paraoxonase 2 expression in patients with hypercholesterolemia is the result of their increased cellular cholesterol content: effect of atorvastatin therapy. Arterioscler Thromb Vasc Biol 2004;24:175–180.
25.
Switzer JA, Hess DC: Statins in stroke: prevention, protection and recovery. Expert Rev Neurother 2006;6:195–202.
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