Genetic Polymorphisms of Superoxide Dismutase 1 and Its Relationship to Diabetic Neuropathy and Nephropathy in Patients with Type 2 Diabetes Mellitus in Ahvaz, Iran

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Department of Genetics, Noor Genetics Lab, Ahvaz, Iran

3 Assistant Professor, Department of Internal Medicine, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Assistant Professor, Department of Urology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

5 Department of Biochemistry, Noor Genetics Lab, Ahvaz, Iran

Abstract

Background: Diabetes is the most prevalent non-infectious disorder of endocrine glands with an increasing rate of incidence. Several people with this type of disease suffer from diabetic retinopathy and nephropathy. Oxidative stress is involved in the path physiology of diabetic nephropathy and retinopathy. The superoxide dismutase (SOD) enzymes play a major role in detoxification of reactive oxygen species and have a protective effect against diabetic nephropathy and retinopathy. Several studies claimed that the polymorphisms of this gene have a key-role in tissue damage results from diabetes.Methods: In the present study, two SNPs in SOD1 gene were analyzed in 145 patients with type 2 diabetes mellitus in Ahvaz, Iran. Blood samples of the patients and 145 individuals without diabetes as controls were collected. DNA was extracted and the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was performed.Findings: For the rs2070424 polymorphism, there were significant differences between the patients who suffer from nephropathy and the control group (P = 0.005; χ2 = 7.55); but no significant difference in the rate of this gene polymorphism between the patients with retinopathy and the control group was seen. The analysis of rs2234694 polymorphism showed that all individuals with and without diabetes had AA genotype. Therefore, it was impossible to perform any statistical test to determine the relationship of this polymorphism and diabetic nephropathy or retinopathy.Conclusion: Understanding the role of polymorphisms of SOD1 gene to modify the course of retinopathy could be an important target for future pharmacological interventions.

Keywords

References

  1. Qiao Q, Hu G, Tuomilehto J, Nakagami T, Balkau B, Borch-Johnsen K, et al. Age- and sex-specific prevalence of diabetes and impaired glucose regulation in 11 Asian cohorts. Diabetes Care 2003; 26(6): 1770-80.
  2. Shuldiner AR, Yang R, Gong DW. Resistin, obesity and insulin resistance--the emerging role of the adipocyte as an endocrine organ. N Engl J Med 2001; 345(18): 1345-6.
  3. Bloomgarden ZT. Insulin resistance: causes and consequences. Int Rev Neurobiol 2005; 65: 1-24.
  4. Hegele RA, Pollex RL. Genetic and physiological insights into the metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 2005; 289(3): R663-R669.
  5. Beaglehole R, Bonita R. Reinvigorating public health. Lancet 2000; 356(9232): 787-8.
  6. Ostbye T, Welby TJ, Prior IA, Salmond CE, Stokes YM. Type 2 (non-insulin-dependent) diabetes mellitus, migration and westernisation: the Tokelau Island Migrant Study. Diabetologia 1989; 32(8): 585-90.
  7. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54(6): 1615-25.
  8. The World Health Report 1997--conquering suffering, enriching humanity. World Health Forum 1997; 18(3-4): 248-60.
  9. Camacho P, Pitale S, Abraira C. Beneficial and detrimental effects of intensive glycaemic control, with emphasis on type 2 diabetes mellitus. Drugs Aging 2000; 17(6): 463-76.
  10. Parving HH, Andersen S, Jacobsen P, Christensen PK, Rossing K, Hovind P, et al. Angiotensin receptor blockers in diabetic nephropathy: renal and cardiovascular end points. Semin Nephrol 2004; 24(2): 147-57.
  11. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 1998; 105(10): 1801-15.
  12. Hallman DM, Huber JC, Jr., Gonzalez VH, Klein BE, Klein R, Hanis CL. Familial aggregation of severity of diabetic retinopathy in Mexican Americans from Starr County, Texas. Diabetes Care 2005; 28(5): 1163-8.
  13. Taverna MJ. Genetics of diabetic complications: retinopathy. Ann Endocrinol (Paris ) 2004; 65(1 Suppl): S17-S25.
  14. Amano S, Yamagishi S, Koda Y, Tsuneoka M, Soejima M, Okamoto T, et al. Polymorphisms of sorbitol dehydrogenase (SDH) gene and susceptibility to diabetic retinopathy. Med Hypotheses 2003; 60(4): 550-1.
  15. Marchler-Bauer A, Anderson JB, Derbyshire MK, DeWeese-Scott C, Gonzales NR, Gwadz M, et al. CDD: a conserved domain database for interactive domain family analysis. Nucleic Acids Res 2007; 35(Database issue): D237-D240.
  16. Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404(6779): 787-90.
  17. DeRubertis FR, Craven PA, Melhem MF. Acceleration of diabetic renal injury in the superoxide dismutase knockout mouse: effects of tempol. Metabolism 2007; 56(9): 1256-64.
  18. Fujita H, Fujishima H, Chida S, Takahashi K, Qi Z, Kanetsuna Y, et al. Reduction of renal superoxide dismutase in progressive diabetic nephropathy. J Am Soc Nephrol 2009; 20(6): 1303-13.
  19. Mollsten A, Marklund SL, Wessman M, Svensson M, Forsblom C, Parkkonen M, et al. A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy. Diabetes 2007; 56(1): 265-9.
  20. Azimi-Nezhad M, Ghayour-Mobarhan M, Parizadeh MR, Safarian M, Esmaeili H, Parizadeh SM, et al. Prevalence of type 2 diabetes mellitus in Iran and its relationship with gender, urbanisation, education, marital status and occupation. Singapore Med J 2008; 49(7): 571-6.
  21. Goldstein BJ. Insulin resistance: from benign to type 2 diabetes mellitus. Rev Cardiovasc Med 2003; 4(Suppl 6): S3-10.
  22. Klein BE, Klein R, Moss SE. Prevalence of cataracts in a population-based study of persons with diabetes mellitus. Ophthalmology 1985; 92(9): 1191-6.
  23. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 1984; 102(4): 527-32.
  24. Lee SC, Lee ET, Kingsley RM, Wang Y, Russell D, Klein R, et al. Comparison of diagnosis of early retinal lesions of diabetic retinopathy between a computer system and human experts. Arch Ophthalmol 2001; 119(4): 509-15.
  25. Massin P, Allouch C, Haouchine B, Metge F, Paques M, Tangui L, et al. Optical coherence tomography of idiopathic macular epiretinal membranes before and after surgery. Am J Ophthalmol 2000; 130(6): 732-9.
  26. Looker HC, Krakoff J, Knowler WC, Bennett PH, Klein R, Hanson RL. Longitudinal studies of incidence and progression of diabetic retinopathy assessed by retinal photography in pima indians. Diabetes Care 2003; 26(2): 320-6.
  27. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Arch Ophthalmol 1994; 112(9): 1217-28.
  28. Liu QZ, Pettitt DJ, Hanson RL, Charles MA, Klein R, Bennett PH, et al. Glycated haemoglobin, plasma glucose and diabetic retinopathy: cross-sectional and prospective analyses. Diabetologia 1993; 36(5): 428-32.
  29. Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, Clermont A, Leitges M, Marette A, et al. Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat Med 2009; 15(11): 1298-306.
  30. McCord JM, Edeas MA. SOD, oxidative stress and human pathologies: a brief history and a future vision. Biomed Pharmacother 2005; 59(4): 139-42.
  31. Panduru NM, Cimponeriu D, Cruce M, Ion DA, Mota E, Mota M, et al. Association of +35A/C (intron3/exon3) polymorphism in SOD1-gene with diabetic nephropathy in type 1 diabetes. Rom J Morphol Embryol 2010; 51(1): 37-41.
  32. Dong A, Shen J, Krause M, Akiyama H, Hackett SF, Lai H, et al. Superoxide dismutase 1 protects retinal cells from oxidative damage. J Cell Physiol 2006; 208(3): 516-26.
Journal of Isfahan Medical School
Volume 32, Issue 280 - Serial Number 280
March and April 2014
Pages 442-452

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History

  • Receive Date: 28 January 2014
  • Revise Date: 01 June 2024
  • Accept Date: 06 April 2022

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