The Role of PON1 Variants in Disease Susceptibility in a Turkish Population

Mahmoud Abudayyak; Tuğçe Boran; Rumeysa Tukel; Ezgi Oztas; Gül Özhan

doi:10.1055/s-0040-1715568

Global Medical Genetics, Inhaltsverzeichnis

CC BY 4.0 · Glob Med Genet 2020; 07(02): 041-046
DOI: 10.1055/s-0040-1715568

Original Article

The Role of PON1 Variants in Disease Susceptibility in a Turkish Population

Mahmoud Abudayyak

¹Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey

,

Tuğçe Boran

¹Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey

,

Rumeysa Tukel

¹Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey

,

Ezgi Oztas

¹Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey

,

Gül Özhan

¹Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey

› Institutsangaben

Abstract

Paraoxonase 1 (PON1) enzyme plays a major role in antioxidant defense and protects the cells against reactive species. The most common PON1 Q192R and L55M polymorphisms are responsible for a wide variation of PON1 activity, which showed an up to 13-fold interindividual variation among the same genotype. PON1 genotypes were evaluated with the development of pancreatitis, colorectal cancer, and hypothyroidism in a hospital-based, case-control study. Individuals with rs662 G allele had a two-fold risk of developing hypothyroidism. A weak association was found between rs854560 T allele and pancreatitis. The results were preliminary. Further studies with a larger number and detailed biochemical parameters are needed.

Keywords

paraoxonase-1 - hypothyroidism - pancreatitis

Volltext

Referenzen

References
1 Başkol G, Köseoğlu K. Paraoxanase: biochemical features, functions and clinical importance. Erciyes Med J 2004; 26: 75-80
2 Harel M, Aharoni A, Gaidukov L. , et al. Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 2004; 11 (05) 412-419
3 Aşkar TK, Büyükleblebici O. Paraoxonase: A new biochemical marker of oxidant-antioxidant status in atherosclerosis. In: Lushchak V. , ed. Oxidative Stress-Molecular Mechanisms and Biological Effects. Intech Open, London: 2012: 145-154
4 Draganov DI, La Du BN. Pharmacogenetics of paraoxonases: a brief review. Naunyn Schmiedebergs Arch Pharmacol 2004; 369 (01) 78-88
5 Ng CJ, Shih DM, Hama SY, Villa N, Navab M, Reddy ST. The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 2005; 38 (02) 153-163
6 Rochu D, Chabrière E, Masson P. Paraoxonase-1 and its interactions with HDL: molecular structures of PON1 and HDL. In: The HDL Handbook. Cambridge: Academic Press; 2010: 99-131
7 Ng CJ, Wadleigh DJ, Gangopadhyay A. , et al. 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 (48) 44444-44449
8 Camps J, Marsillach J, Joven J. The paraoxonases: role in human diseases and methodological difficulties in measurement. Crit Rev Clin Lab Sci 2009; 46 (02) 83-106
9 Abelló D, Sancho E, Camps J, Joven J. Exploring the role of paraoxonases in the pathogenesis of coronary artery disease: a systematic review. Int J Mol Sci 2014; 15 (11) 20997-21010
10 Aviram M, Rosenblat M. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 2004; 37 (09) 1304-1316
11 Garin MC, James RW, Dussoix P. , et al. Paraoxonase polymorphism Met-Leu54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased risk of cardiovascular disease in diabetes. J Clin Invest 1997; 99 (01) 62-66
12 Leviev I, Deakin S, James RW. Decreased stability of the M54 isoform of paraoxonase as a contributory factor to variations in human serum paraoxonase concentrations. J Lipid Res 2001; 42 (04) 528-535
13 Mackness M, Mackness B. Human paraoxonase-1 (PON1): gene structure and expression, promiscuous activities and multiple physiological roles. Gene 2015; 567 (01) 12-21
14 Davies HG, Richter RJ, Keifer M, Broomfield CA, Sowalla J, Furlong CE. The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin. Nat Genet 1996; 14 (03) 334-336
15 Mackness MI, Arrol S, Mackness B, Durrington PN. Alloenzymes of paraoxonase and effectiveness of high-density lipoproteins in protecting low-density lipoprotein against lipid peroxidation. Lancet 1997; 349 (9055): 851-852
16 Li HL, Liu DP, Liang CC. Paraoxonase gene polymorphisms, oxidative stress, and diseases. J Mol Med (Berl) 2003; 81 (12) 766-779
17 Tarcin O, Yavuz DG. Paraoxonase 1 activity in endocrine diseases. Turk J Endocrinol Metab 2011; 15: 33-38
18 Kondo I, Yamamoto M. Genetic polymorphism of paraoxonase 1 (PON1) and susceptibility to Parkinson's disease. Brain Res 1998; 806 (02) 271-273
19 Scacchi R, Gambina G, Martini MC, Broggio E, Vilardo T, Corbo RM. Different pattern of association of paraoxonase Gln192-->Arg polymorphism with sporadic late-onset Alzheimer's disease and coronary artery disease. Neurosci Lett 2003; 339 (01) 17-20
20 Sarandöl E, Taş S, Dirican M, Serdar Z. Oxidative stress and serum paraoxonase activity in experimental hypothyroidism: effect of vitamin E supplementation. Cell Biochem Funct 2005; 23 (01) 1-8
21 Costantini F, Pierdomenico SD, De Cesare D. , et al. Effect of thyroid function on LDL oxidation. Arterioscler Thromb Vasc Biol 1998; 18 (05) 732-737
22 Dumitriu L, Bartoc R, Ursu H, Purice M, Ionescu V. Significance of high levels of serum malonyl dialdehyde (MDA) and ceruloplasmin (CP) in hyper- and hypothyroidism. Endocrinologie 1988; 26 (01) 35-38
23 Baskol G, Atmaca H, Tanriverdi F, Baskol M, Kocer D, Bayram F. Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. Exp Clin Endocrinol Diabetes 2007; 115 (08) 522-526
24 Van Der Logt EM, Janssen CH, Van Hooijdonk Z. , et al. No association between genetic polymorphisms in NAD(P)H oxidase p22phox and paraoxonase 1 and colorectal cancer risk. Anticancer Res 2005; 25 (2B): 1465-1470
25 Franco-Pons N, Marsillach J, Joven J, Camps J, Closa D. Serum paraoxonase undergoes inhibition and proteolysis during experimental acute pancreatitis. J Gastrointest Surg 2008; 12 (05) 891-899
26 Kumon Y, Nakauchi Y, Suehiro T. , et al. Proinflammatory cytokines but not acute phase serum amyloid A or C-reactive protein, downregulate paraoxonase 1 (PON1) expression by HepG2 cells. Amyloid 2002; 9 (03) 160-164
27 Aynacioglu AS, Cascorbi I, Mrozikiewicz PM, Nacak M, Tapanyigit EE, Roots I. Paraoxonase 1 mutations in a Turkish population. Toxicol Appl Pharmacol 1999; 157 (03) 174-177
28 Zama T, Murata M, Matsubara Y. , et al. A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese. Arterioscler Thromb Vasc Biol 1997; 17 (12) 3565-3569
29 Sanghera DK, Saha N, Kamboh MI. The codon 55 polymorphism in the paraoxonase 1 gene is not associated with the risk of coronary heart disease in Asian Indians and Chinese. Atherosclerosis 1998; 136 (02) 217-223
30 Özhan G, Topal P, Alpertunga B. Flavin-containing monooxygenase 3 gene polymorphisms in Turkish population. Toxicol Mech Methods 2012; 22 (06) 461-465
31 Arici M, Özhan G. The genetic profiles of CYP1A1, CYP1A2 and CYP2E1 enzymes as susceptibility factor in xenobiotic toxicity in Turkish population. Saudi Pharm J 2017; 25 (02) 294-297
32 Akçay YD, Sagin FG, Sendağ F, Oztekin K, Sozmen EY. Effects of estrogen-only therapy on LDL oxidation in women with hysterectomy: does paraoxonase genotype play a role?. Maturitas 2006; 53 (03) 325-332
33 Gupta N, Gill K, Singh S. Paraoxonases: structure, gene polymorphism & role in coronary artery disease. Indian J Med Res 2009; 130 (04) 361-368
34 Humbert R, Adler DA, Disteche CM, Hassett C, Omiecinski CJ, Furlong CE. The molecular basis of the human serum paraoxonase activity polymorphism. Nat Genet 1993; 3 (01) 73-76
35 Zargari M, Sharafeddin F, Mahrooz A, Alizadeh A, Masoumi P. The common variant Q192R at the paraoxonase 1 (PON1) gene and its activity are responsible for a portion of the altered antioxidant status in type 2 diabetes. Exp Biol Med (Maywood) 2016; 241 (14) 1489-1496
36 Ergun MA, Yurtcu E, Demirci H. , et al. PON1 55 and 192 gene polymorphisms in type 2 diabetes mellitus patients in a Turkish population. Biochem Genet 2011; 49 (1-2): 1-8
37 Altuner D, Suzen SH, Ates I, Koc GV, Aral Y, Karakaya A. Are PON1 Q/R 192 and M/L 55 polymorphisms risk factors for diabetes complications in Turkish population?. Clin Biochem 2011; 44 (5-6): 372-376
38 Stevens VL, Rodriguez C, Talbot JT, Pavluck AL, Thun MJ, Calle EE. Paraoxonase 1 (PON1) polymorphisms and prostate cancer in the CPS-II Nutrition Cohort. Prostate 2008; 68 (12) 1336-1340
39 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 (03) 240-251
40 Saadat M. Paraoxonase 1 genetic polymorphisms and susceptibility to breast cancer: a meta-analysis. Cancer Epidemiol 2012; 36 (02) e101-e103
41 Unal E, Uzun H, Kusaslan R. , et al. Serum paraoxonase (a high-density lipoprotein-associated lipophilic antioxidant) activity and lipid profile in experimental acute pancreatitis. Pancreas 2005; 31 (01) 84-87
42 Verlaan M, Harbers EG, Pap A, Jansen JB, Peters WH, Drenth JP. Paraoxonase 1-192Q allele is a risk factor for idiopathic chronic pancreatitis. Mol Diagn 2005; 9 (01) 9-15
43 Duntas LH. Thyroid disease and lipids. Thyroid 2002; 12 (04) 287-293
44 Sundaram V, Hanna AN, Koneru L, Newman HA, Falko JM. Both hypothyroidism and hyperthyroidism enhance low density lipoprotein oxidation. J Clin Endocrinol Metab 1997; 82 (10) 3421-3424
45 Yavuz DG, Yüksel M, Deyneli O, Ozen Y, Aydin H, Akalin S. Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients. Clin Endocrinol (Oxf) 2004; 61 (04) 515-521
46 Azizi F, Raiszadeh F, Solati M, Etemadi A, Rahmani M, Arabi M. Serum paraoxonase 1 activity is decreased in thyroid dysfunction. J Endocrinol Invest 2003; 26 (08) 703-709
47 Aviram M, Rosenblat M, Billecke S. , et al. Human serum paraoxonase (PON 1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants. Free Radic Biol Med 1999; 26 (7-8): 892-904