Genetic Variation in SOD1Gene Promoter Ins/Del and Its Influence on Oxidative Stress in Beta Thalassemia Major Patients
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Abstract
Objective: A genetic polymorphism of 50 bp insertion/deletion (Ins/Del) (rs 36232792) in the promoter region of the SOD1 was reported to influence the enzyme activity. The aims of the present study are to evaluate the status of this polymorphism on the SOD1 levels in human peripheral blood cells and its association with risk of oxidative stress in beta thalassemia major patients.
Material and Methods: The study was carried out on 200 thalassemia major patients and 200 healthy controls healthy. The SOD1 genotypes were determined using a polymerase chain reaction (PCR)-based method. Serum SOD activity were assessed using SOD assay kit. In-silico analysis was assessed using loss-of-function (LofTool) (PMID: 27563026).
Results: No association was found between the insertion/deletion (Ins/Del) polymorphism of SOD1 and risk of oxidative stress in thalassemia major patients
Conclusion: The results of this study indicated that the oxidative sterss is not affected by the Ins/ Del polymorphism of SOD1 in thalassemia major patients. Further research with larger samples size and with other genes of antioxidant system is required.
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16. Dreger H, Westphal K, Weller A, et al. Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection. Cardiovasc Res. 2009;83(2):354-61
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18. Chen H, Yu M, Li M, et al. Polymorphic variations in manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) contribute to elevated plasma triglyceride levels in Chinese patients with type 2 diabetes or diabetic cardiovascular disease. Mol Cell Biochem. 2012; 363(1-2):85-91.
19. Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal. 2011; 15(6):1583-606.
20. Verreth W, De Keyzer D, Davey PC, et al. Rosuvastatin restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice. Br J Pharmacol. 2007; 151(3):347-55.
21. Milani P, Gagliardi S, Bongioanni P, et al. Effect of the 50 bp deletion polymorphism in the SOD1 promoter on SOD1 mRNA levels in Italian ALS patients. J Neurol Sci. 2012; 313(1-2):75-8.
22. Flekac M, Skrha J, Hilgertova J, et al. Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus. BMC Med Genet. 2008; 9:30.
23. Wang XL, Duarte N, Cai H, et al. Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease in the Australian hospitalbased population. Atherosclerosis. 1999; 146(1):133-40.
24. Yuan N, Zhang F, Zhang LL, et al. SOD1 gene transfer into paraventricular nucleus attenuates hypertension and sympathetic activity in spontaneously hypertensive rats. Pflugers Arch. 2013; 465(2):261-70.
25. Gordon T, Tyreman N, Li S, et al. Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis. 2010; 37(2):412-22.
26. Montano MA, Barrio Lera JP, Gottlieb MG, et al. Association between manganese superoxide dismutase (MnSOD) gene polymorphism and elderly obesity. Mol Cell Biochem. 2009; 328(1-2):33-40.
27. Kretowski A, Hokanson JE, McFann K, et al. The apolipoprotein A-IV Gln360His polymorphism predicts progression of coronary artery calcification in patients with type 1 diabetes. Diabetologia. 2006; 49(8):1946-54.
28. Saify K, Saadat M. Influence of a 50bp Ins/Del polymorphism at promoter of the superoxide dismutase-1 on gene expression and risk of heroin dependency. Environ Health Prev Med. 2017; 22:4.
29. Zendehboodi Z. Association between 50 bp insertion/ deletion polymorphism in promoter of the superoxide dismutase-1 and temperament. Int J Basic Sci Med. 2018; 3(2):59- 62.
2. Ghone RA, Kumbar KM, Suryakar AN, et al. oxidative stress and disturbance in antioxidant balance in beta thalassemia major. Indian J Clin Biochem. 2008; 23(4):337-40.
3. Eskandari-Nasab E, Kharazi-Nejad E, Nakhaee A, et al. 50-bp Ins/Del Polymorphism of SOD1 is Associated with Increased Risk of Cardiovascular Disease . Acta Med Iran. 2014; 52(8):591-5.
4. Milani P, Gagliardi S, Cova E, et al. SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS. Neurol Res Int. 2011; 2011: 458427.
5. Grinberg LN, Rachmilewitz EA, Chevion M, et al. Hydroxyl radical generation in β-thalassemic red blood cells. Free Radic Biol Med. 1995; 18(3):611-5.
6. Shanaki M, Ehteram H, Nasiri H, et al. Assessment of Liver and Kidney Functional Parameters along with Oxidative Stress and Inflammatory Biomarker in Patients with β- Thalassemia Major. Iran J Ped Hematol Oncol. 2016; 6(4): 249-260
7. Afonso V, Santos G, Collin P, et al. Tumor necrosis factor-α down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway. Free Radic Biol Med. 2006; 41(5):709-21.
8. Forsberg L, Faire U, Morgenstern R. Oxidative stress, human genetic variation, and disease. Arch Biochem Biophys. 2001; 389(1):84-93.
9. Tang H, Dong X, Day RS, et al. Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer. Carcinogenesis. 2010; 31(4):607-613.
10. Juronen E, Tasa G, Veromann S, et al. Polymorphic Glutathione S-Transferases as Genetic Risk Factors for Senile Cortical Cataract in Estonians. Invest Ophthalmol Vis Sci. 2000; 41(8):2262-7.
11. Rajkumar S, Praveen MR, Gajjar D, et al. Activity of superoxide dismutase isoenzymes in lens epithelial cells derived from different types of age-related cataract. J Cataract Refract Surg. 2008; 34(3):470-4.
12. Zhang Yi, Zhang L, Sun D, et al. Genetic polymorphisms of superoxide dismutases, catalase, and glutathione peroxidase in age-related cataract. Mol Vis. 2011; 17: 2325–2332.
13. Neves AL, Mohammedi K, Emery N, et al. Allelic variations in superoxide dismutase-1 (SOD1) gene and renal and cardiovascular morbidity and mortality in type 2 diabetic subjects. Mol Genet Metab. 2012; 106(3):359-65.
14. Holvoet P. Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg. 2008; 70(3):193-219.
15. Yan SF, Ramasamy R, Schmidt AM. The RAGE axis: a fundamental mechanism signaling danger to the vulnerable vasculature. Circ Res. 2010; 106(5):842-853.
16. Dreger H, Westphal K, Weller A, et al. Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection. Cardiovasc Res. 2009;83(2):354-61
17. Lee S, Park Y, Zhang C. Exercise Training Prevents Coronary Endothelial Dysfunction in Type 2 Diabetic Mice. Am J Biomed Sci. 2011; 3(4): 241–252.
18. Chen H, Yu M, Li M, et al. Polymorphic variations in manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPX1), and catalase (CAT) contribute to elevated plasma triglyceride levels in Chinese patients with type 2 diabetes or diabetic cardiovascular disease. Mol Cell Biochem. 2012; 363(1-2):85-91.
19. Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal. 2011; 15(6):1583-606.
20. Verreth W, De Keyzer D, Davey PC, et al. Rosuvastatin restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice. Br J Pharmacol. 2007; 151(3):347-55.
21. Milani P, Gagliardi S, Bongioanni P, et al. Effect of the 50 bp deletion polymorphism in the SOD1 promoter on SOD1 mRNA levels in Italian ALS patients. J Neurol Sci. 2012; 313(1-2):75-8.
22. Flekac M, Skrha J, Hilgertova J, et al. Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus. BMC Med Genet. 2008; 9:30.
23. Wang XL, Duarte N, Cai H, et al. Relationship between total plasma homocysteine, polymorphisms of homocysteine metabolism related enzymes, risk factors and coronary artery disease in the Australian hospitalbased population. Atherosclerosis. 1999; 146(1):133-40.
24. Yuan N, Zhang F, Zhang LL, et al. SOD1 gene transfer into paraventricular nucleus attenuates hypertension and sympathetic activity in spontaneously hypertensive rats. Pflugers Arch. 2013; 465(2):261-70.
25. Gordon T, Tyreman N, Li S, et al. Functional over-load saves motor units in the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis. 2010; 37(2):412-22.
26. Montano MA, Barrio Lera JP, Gottlieb MG, et al. Association between manganese superoxide dismutase (MnSOD) gene polymorphism and elderly obesity. Mol Cell Biochem. 2009; 328(1-2):33-40.
27. Kretowski A, Hokanson JE, McFann K, et al. The apolipoprotein A-IV Gln360His polymorphism predicts progression of coronary artery calcification in patients with type 1 diabetes. Diabetologia. 2006; 49(8):1946-54.
28. Saify K, Saadat M. Influence of a 50bp Ins/Del polymorphism at promoter of the superoxide dismutase-1 on gene expression and risk of heroin dependency. Environ Health Prev Med. 2017; 22:4.
29. Zendehboodi Z. Association between 50 bp insertion/ deletion polymorphism in promoter of the superoxide dismutase-1 and temperament. Int J Basic Sci Med. 2018; 3(2):59- 62.
| Files | ||
| Issue | Vol 14, No 2 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v14i2.2674 | |
| Keywords | ||
| Thalassemia; Superoxide dismutase-1; Polymorphism; Hemoglobin | ||
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How to Cite
1.
Tripathi P, Agarwal S, Sarangi A. Genetic Variation in SOD1Gene Promoter Ins/Del and Its Influence on Oxidative Stress in Beta Thalassemia Major Patients. Int J Hematol Oncol Stem Cell Res. 2020;14(2):110-117.
