Paraoxonase 1 Phenotype and Paraoxonase Activity in Asthmatic Patients
Abstract
Oxidative stress is involved in the pathogenesis of asthma. Paraoxonase 1 (PON1) and arylesterase are esterase enzymes displaying antioxidant characteristics. PON1 activity varies widely among individuals and ethnic groups, partly related to polymorphisms. The aim of this study was to determine the activities of PON1 and arylesterase including the phenotype distribution of PON1 in asthmatic patients and healthy subjects. Forty-nine asthmatic patients and 41 healthy people were included in this study. Serum PON1 and arylesterase activities were determined by spectrophotometric assays, as well as the lipid profiles. The PON1 ratio (salt stimulated paraoxonase/arylesterase) was trimodally distributed and this ratio was used to determine the individual phenotypes of all subjects. The PON1 activity in the asthmatic patients was significantly lower (p=0.024) when compared to the healthy control group, however no significant difference in the activity of arylesterase was observed between the two groups. The prevalence of the PON1 phenotypes in the asthmatic population were 26.5%, 16.3% and 57.2 % for QQ, QR and RR, respectively. PON1 activity was significantly lower in asthmatic patients; in addition, the results of this investigation indicated that PON1 RR phenotype may be an important risk factor in asthma disease.
1. Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat Med 2012;18(5):716-25.
2. Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: A new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011; 127(2):355-60.
3. Kauffmann F, Demenais F. Gene-environment interactions in asthma and allergic diseases: Challenges and perspectives. J Allergy Clin Immunol 2012; 130(6):1229-40.
4. Ahmad A, Shameem M, Husain Q. Relation of oxidant- antioxidant imbalance with disease progression in patients with asthma. Ann Thorac Med 2012; 7(4):226-32.
5. Ciencewicki J, Trivedi S, Kleeberger SR. Oxidants and the pathogenesis of lung diseases. J Allergy Clin Immunol 2008; 122(3):456–68.
6. Riedl MA, Nel AE. Importance of oxidative stress in the pathogenesis and treatment of asthma. Curr Opin Allergy Clin Immunol 2008; 8(1):49–56.
7. Kappelle PJ, de Boer JF, Perton FG, Annema W, de Vries R, Dullaart RP, et al. Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL. Eur J Clin Invest 2012; 42(5):487-95.
8- Costa LG, Cole TB, Jarvik GP, Furlong CE. Functional genomic of the paraoxonase (PON1) polymorphisms: effects on pesticide sensitivity, cardiovascular disease, and drug metabolism. Annu Rev Med 2003; 54:371-92.
9- Vaisi-Raygani A, Ghaneialvar H, Rahimi Z, Tavilani H, Pourmotabbed T, Ebrahim Shakiba E, et al. Paraoxonase Arg 192 allele is an independent risk factor for three- vessel stenosis of coronary artery disease. Mol Biol Rep 2011; 38(8):5421-8.
10-Bahrehmand F, Vaisi-Raygani A, Ahmadi R, Kiani A, Rahimi Z, Tavilani H, et al. Paraoxonase (PON1) 55 polymorphism and association with systemic lupus erythematosus. Iran J Allergy Asthma Immunol 2013;12(3): 211-19.
11- Bahrehmand F, Vaisi-Raygani A, Rahimi Z, Ahmadi R, Kiani A, Tavilani H, et al. Synergistic effects of BuChE non-UU phenotype and paraoxonase (PON1) 55 M allele on the risk of systemic lupus erythematosus: influence on lipid and lipoprotein metabolism and oxidative stress, preliminary report. Lupus 2014; 23(3):263-72.
12. Asefi M1, Vaisi-Raygani A, Bahrehmand F, Kiani A,Rahimi Z, Nomani H, et al. Pourmotabbed. Paraoxonase 1 (PON1) 55 polymorphism, lipid profiles and psoriasis. Br J Dermatol 2012; 167(6):1279-86.
13. GINA Report, Global Strategy for Asthma Management and Prevention. 2011. Updated 2011. http://www.ginasthma.org/uploads/users/files/GINA_Rep ort2011_May4.
14. Gan KN, Smolen A, Eckerson HW, La Du BN.Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos 1991; 19(1):100–6.
15. Paragh G, Asztalos L, Seres I, Balogh Z, Löcsey L, Kárpáti I, et al. Serum paraoxonase activity changes in uremic and kidney-transplanted patients. Nephron 1999;83(2):126–31.
16. Miller NE, La Ville A, Crook D. Direct evidence that reverse cholesterol transport is mediated by high-density lipoprotein in rabbit. Nature 1985; 314(6006):109–11.
17. La Du BN, Eckerson HW. The polymorphic paraoxonase/arylesterase isozymes of human serum. Fed Proc 1984; 43(8):2338–41.
18. Çakmak A, Zeyrek D, Atas A, Selek S, Erel O. Oxidative status and paraoxonase activity in children with asthma. Clin Invest Med 2009; 32(5):327-34.
19. Ekmekci OB, Donma O, Ekmekci H, Yildirim N, Uysal O, Sardogan E, et al. Plasma Paraoxonase Activities, Lipoprotein Oxidation, and Trace Element Interaction in Asthmatic Patients. Biol Trace Elem Res 2006; 111(1-3):41-52.
20. Gornicka G, Beltowski J, Wojcicka G, Jamroz A. Serum paraoxonase activity, total antioxidant potential and lipid peroxidation products in children with bronchial asthma exacerbation. Wiad Lek 2002; 55(5-6):257-63.
21. Tölgyesi G, Molnár V, Semsei AF, Kiszel P, Ungvári I, Pócza P, et al. Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease. Int Immunol 2009; 21(8):967-75.
22. Aviram M, Rosenblat M, Billecke S, Erogul J, Sorenson R, Bisgaier CL, et al. Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999;26(7-8):892-904.
23. Polonikov AV, Ivanov VP, Solodilova MA. Genetic variation of genes for xenobiotic-metabolizing enzymes and risk of bronchial asthma: The importance of gene– gene and gene–environment interactions for disease susceptibility. J Hum Genet 2009; 54(8):440–9.
24. Mohamed RH, Karam RA, El-Aziz TA. The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease. Clin Biochem 2010;43(6):553-8.
25. Hegele RA, Brunt JH, Connelly PW. A polymorphism of the paraoxonase gene associated with variation in plasma lipoproteins in a genetic isolate. Arterioscler Thromb Vasc Biol 1995; 15(1):89-95.
26. Watzinger N, Schmidt H, Schumacher M, Schmidt R, Eber B, Fruhwald FM, et al. Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: A community-based study. Cardiology 2002; 98(3):116-22.
27. Mackness B, Davies GK, Turkie W, Lee E, Roberts DH, Hill E, et al. Paraoxonase status in coronary heart disease: are activity and concentration more important than genotype? Arterioscler Thromb Vasc Biol 2001;21(9):1451-7.
28. Bonafè M, Marchegiani F, Cardelli M, Olivieri F, Cavallone L, Giovagnetti S, et al. Genetic analysis of paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians. Eur J Hum Genet 2002; 10(5):292-6.
29. Jarvik GP, Rozek LS, Brophy VH, Hatsukami TS, Richter RJ, Schellenberg GD, et al. Paraoxonase (PON1) phenotype is a better predictor of vascular disease than is PON1192 or PON155 genotype. Arterioscler Tromb Vas Biol 2000; 20(11):2441-7.
30. Vincent-Viry M, Sass C, Bastien S, Aguillon D, Siest G, Visvikis S. PON1-192 phenotype and genotype assessments in 918 subjects of the Stanislas cohort study. Clin Chem Lab Med 2003; 41(4):535-40.
31. Teiber JF, Kramer GL, Haley RW. Methods for Measuring Serum Activity Levels of the 192 Q and R Isoenzymes of Paraoxonase 1 in QR Heterozygous Individuals. Clin Chem 2013; 59(8):1251-9.
32. Richter RJ, Jarvik GP, Furlong CE. Paraoxonase 1 status as a risk factor for disease or exposure. Adv Exp Med Biol 2010; 660:29-35.
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Issue | Vol 14, No 1 (2015) | |
Section | Articles | |
Keywords | ||
Arylesterase Asthma Paraoxonase 1 Phenotype |
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