Distribution of Paraoxonase 1 polymorphisms and activities in obese patients

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Study objective. The objective of this study was to investigate PON1 phenotype and genotype in Romanian patients with abdominal obesity. Materials and methods. The study groups consisted of 88 patients with abdominal obesity and 46 subjects with normal waist circumference, matched for age and gender. For each patient, we determined the clinical parameters that may influence PON1 activities. Q192R and L55M polymorphisms analysis in the PON1 gene were performed by PCR-RFLP using specific primers and restriction enzymes. PON1 lactonase, paraoxonase and arylesterase activities were assayed by spectrophotometric methods. Analysis of PON1 genotypes and activities distribution in the obese and non-obese individuals was performed with Med- Calc Software (Version Results. There was no statistically significant difference between obese and controls in regards to age and gender. The study revealed that PON1 activities were not influenced by gender. Of all PON1 activities, only the paraoxonase activity was inversely correlated with age, being significantly reduced in patients with abdominal obesity compared to non-obesity (p=0.009). Abdominal circumference independently influenced only the variation of arylesterase activity (R2=6.5%, p=0.003). Distribution of PON1 genotypes in the study groups was significantly different (p=0.007) only for the Q192R but not for the L55M genotypes. The QR genotype had the highest influence on paraoxonase activity (R2=40.6; p<0.001). The MM genotype had the greatest influence on arylesterase (R2=11.3%, p<0.001) and lactonase activities (R2=7.4%, p<0.001). Conclusions. Q192R genotypes distribution was significantly different in obese patients and the QR genotype influenced greatly the paraoxonase activity. The MM genotype had the most important independent influence on the lactonase and arylesterase activities .

1. She Z-G, Chen H-Z, Yan Y, Li H, Liu D-P. The Human Paraoxonase Gene Cluster as a Target in the Treatment of Atherosclerosis. Antioxid Redox Signal. 2012 Mar 15;16(6):597-632.

2. Kedage V, Muttigi MS, Shetty MS, Suvarna R, Rao SS, Joshi C, et al. Serum Paraoxonase 1 Activity Status in Patients with Liver Disorders. Saudi J Gastroenterol. 2010;16(2):79-83.

3. Beltowski J, Wójcicka G, Jamroz A. Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia. Atherosclerosis. 2003;170:21-9.

4. Audikovszky M, Pados G, Seres I, Harangi M, Fülöp P, Katona E, et al. Orlistat increases serum paraoxonase activity in obese patients. Nutr Metab Cardiovasc Dis. 2007;17:268-73.

5. Veiga L, Silva-Nunes J, Melão A, Oliveira A, Duarte L, Brito M. Q192R polymorphism of the paraoxonase-1 gene as a risk factor for obesity in Portuguese women. Eur J Endocrinol. 2011;164:213-8.

6. Martínez-Salazar MF, Almenares-López D, García- Jiménez S, Sánchez-Alemán MA, Juantorena-Ugás A, Ríos C, et al. Relationship between the paraoxonase (PON1) L55M and Q192R polymorphisms and obesity in a Mexican population: a pilot study. Genes Nutr. 2011;6:361-8.

7. Camps J, Marsillach J, Joven J. Measurement of serum paraoxonase-1 activity in the evaluation of liver function. World J Gastroenterol. 2009;15(16):1929-33.

8. Chedid R, Gannagé-Yared MH, Khalifé S, Halaby G, Zoghbi F. Impact of different metabolic syndrome classifications on the metabolic syndrome prevalence in a young Middle Eastern population. Metabolism. 2009;58(6):746-52.

9. Paşca SP, Dronca E, Nemeş B, Kaucsár T, Endreffy E, Iftene F, et al. Paraoxonase 1 activities and polymorphisms in autism spectrum disorders. J Cell Mol Med. 2010;14:600-7.

10. Altuner D, Ates I, Suzen SH, Koc GV, Aral Y, Karakaya A. The relationship of PON1 QR 192 and LM polymorphisms with serum paraoxonase activities of Turkish diabetic patients. Toxicol Ind Health. 2011;27(10):873-8.

11. Grdic Rajkovic M, Rumora L, Barisic K. The paraoxonase 1,2 and 3 in humans. Biochemia Medica. 2011;21(2):122-30.

12. ATP III Final Report PDF: Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report Circulation. 2002;106:3143.

13. Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the Metabolic Syndrome A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5.

14. WHO. Obesity: preventing and managing the global epidemic. Report of a WHO Consultation. WHO Technical Report Series 894. Geneva: World Health Organization (accessed in February 2013). Available at http://whqlibdoc.who.int/trs/WHO_TRS_894.pdf.

15. Eckerson HW, Romson J, Wyte C, La Du BN. The human serum paraoxonase polymorphism: identification of phenotypes by their response to salts. Am J Hum Genet. 1983;35(2):214-27.

16. Khersonsky O, Tawfik DS. Structure-reactivity studies of serum paraoxonase PON1 suggest that its native activity is lactonase. Biochemistry. 2004;44:6371-82.

17. Gupta N, Singh S, Maturu VN, Sharma YP, Gill KD.Paraoxonase 1 (PON1) polymorphisms, haplotypes and activity in predicting CAD risk in North-West Indian Punjabis. PLoS One. 2011;6(5):e17805.

18. Kotani K, Sakane N, Sano Y, Tsuzaki K, Matsuoka Y, Eqawa K et al. Change on the Physiological Lactonase Activity of Serum Paraoxonase 1 by Diet Intervention for Weight Loss in healthy Overweight and Obese Women. J Clin Biochem Nutr. 2009; 45(3):329-34.

19. Kordi-Tamandani DM, Hashemi M, Sharifi N, Kaykhaei MA, Torkamanzehi A. Association between paraoxonase-1 gene polymorphisms and risk of metabolic syndrome. Mol Biol Rep. 2012;39:937-43.

20. Gorshunskaya MY, Karachentsev YI, Atramentova LA, Tyzhnenko TV, Kravchun NA, Pochernyaev AK, et al. Q192R polymorphism of PON-1 gene in type 2 diabetes patients. Cytol Genet. 2011 Feb 1;45(1):38-40.

21. Costa LG, Vitalone A, Cole TB, Furlong CE. Modulation of paraoxonase (PON1) activity. Biochemical Pharmacology; 2005;69:541-50.

22. Tabur S, Torun AN, Sabuncu T, Turan MN, Celik H, Ocak AR, et al. Non-diabetic metabolic syndrome and obesity do not affect serum paraoxonase and arylesterase activities but do affect oxidative stress and inflammation.Eur J Endocrinol 2011;162(3):535-41.

23. Rogulj D, Konjevoda P, Milić M, Mladinić M, Domijan AM. Fatty liver index as an indicator of metabolic syndrome. Clin Bioche. 2012;45(1-2):68-71.

24. Ferretti G, Bacchetti T, Masciangelo S, Bicchiega V. HDL-paraoxonase and Membrane Lipid Peroxidation: A Comparison Between Healthy and Obese Subjects.Obesity. 2010;18(6):1079-84.

25. Roest M, van Himbergen TM, Barendrecht AB, Peeters PH, van der Schouw YT, Voorbij HA. Genetic and environmental determinants of the PON-1 phenotype. Eur J Clin Invest. 2007;37:187-96.

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

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