The Association of SMUG1 Gene Polymorphism with Age-related Macular Degeneration in Northwestern Iran

Document Type : Original Articles

Authors

Abstract

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss and debilitating disease in old age, which involves the central retina/macula among elderly patients. The genetic and environmental factors have important role in this multifactorial disease. Oxidative stress and DNA damages would have important impact on the onset and progression of AMD.  In this study, the possible association of c.-31A>G (rs3087404) polymorphism in the promoter region of SMUG1 gene with AMD disease was investigated. Fifty five AMD patients and 130 healthy age-, gender- and ethnicity-matched unrelated people as control group were genotyped by restriction fragment length polymorphism PCR (RFLP-PCR). Both groups were from Northwest of Iran (Tabriz).  Statistical analysis showed a significant association of AG genotype of this polymorphism with AMD. These results suggest a possible protective effect of this genotype for AMD disease (P=0.02, OR=0.574) among patients from Northwest of Iran. This genotype was observed more frequently in controls compared to the patients (59.23% v s 45.45%).

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  1. Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med 2008; 358: 2606-2617.
  2. Ratnapriya R, Chew EY. Age-related macular degeneration-clinical review and genetic update. Clinical Genetics 2013: 84: 160-166.
  3. 3. Wang JJ, Rochtchina E, Lee AJ, Chia EM, Smith W, Cumming RG, et al. Ten-year incidence and progression of age-related maculopathy: the blue Mountains Eye Study. Ophthalmology 2007; 114: 92-98.
  4. Axer-Siegel R, Bourla D, Ehrlich R, Dotan G, Benjamini Y, Gavendo S. Association of neovascular age-related macular degeneration and hyperhomocysteinemia. Am J Ophthalmol 2004; 137: 84-89.
  5. Anad R, Bressler SB, Davis MD, Ferris FL, Klein R. Age related eye disease study research group: risk factors associated with age related macular degeneration. A case control study in the age related eye disease study: age related eye disease study report number 3. Ophthalmology 2000; 107: 2224-2232.
  6. Ding X, Patel M, Chan CC. Molecular pathology of age-related macular degeneration. Progress in Retinal and Eye Research 2009;28:1–18.
  7. Szaflik JP, Janik-Papis K, Synowiec E, Ksiazek D, Zaras M, Wozniak K, Szaflik J, Blasiak J. DNA damage and repair in age-related macular degeneration. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 2009;669,169–176.
  8. Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of agerelated macular degeneration. Surv Ophthalmol 2000;45:115–134.
  9. Maynard S, H.Schurman S, Harboe C, Souza-Pinto N and Bohr V. Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis.2009;30, 2-10.
  10. Krokan, H.E.; Drabløs, F.; Slupphaug, G. Uracil in DNA-Occurrence, consequences and repair. Oncogene 2002,21,8935-8948.
  11. Masaoka, A.; Matsubara, M.; Hasegawa, R.; Tanaka, T.; Kurisu, S.; Terato, H.;Ohyama Y.; Karino, N.; Matsuda, A.; Ide, H. Mammalian 5-formyluracil-DNA glycosylase. 2. Role of SMUG1 uracil-DNA glycosylase in repair of 5-formyluracil and other oxidized and deaminated base lesions. Biochemistry 2003, 42, 5003–5012.
  12. Miller SA, Dykes D, Polsky F. A simple salting out procedure for extracting DNA from human nucleatedcells. Nucleic Acids Res 1988;16(3):1215.
  13. Synowiec, E.; Wysokinski, D.; Zaraoe, M.; Kolodziejska, U.; Stoczynska, E.; Janik, K.; Szaflik, J Blasiak, J.; Szaflik, J.P. Association between polymorphism of the DNA repair SMUG1 and UNG genes and age-related macular degeneration. Retina 2014, 34:38-47.
  14. Chen Y, Bedell M, and Zhang K. Age-related Macular Degeneration: Genetic and Environmental Factors of Disease. Molecular interventions, 2010 Oct; 10(5): 271–281.
  15. Chen X, Guo C and Kong J. Oxidative stress in neurodegenerative diseases. Neural Regen Res 2012 Feb 15; 7(5): 376–385.
  16. G. Padma, M. Mamata, K. Ravi Kumar Reddy, T. Padma. Polymorphisms in two DNA repair genes (XPD and XRCC1) – association with age related cataracts. Molecular Vision 2011; 17:127-133
  17. Blasiak J, Synowiec E, Salminen A, Kaarniranta K. Genetic Variability in DNA Repair Proteins in Age-Related Macular Degeneration. International Journal of Molecular Sciences 2012; 13: 13378-13397.
  18. Chanson A, et al. Polymorphisms in uracil-processing genes, but not one-carbon nutrients, are associated with altered DNA uracil concentrations in an urban Puerto Rican population. Am J Clin Nutr 2009;89:1927–36.
  19. Akbari, M.; Otterlei, M.; Peña-Diaz, J.; Krokan, H.E. Different organization of base excision repair of uracil in DNA in nuclei and mitochondria and selective upregulation of mitochondrial uracil-DNA glycosylase after oxidative stress. Neuroscience 2007, 145, 1201–1212.
  20. Marian, C.; Tao, M.; Mason, J.B.; Goerlitz, D.S.; Nie, J.; Chanson, A.; Freudenheim, J.L.;Shields, P.G. Single nucleotide polymorphisms in uracil-processing genes, intake of one-carbon nutrients and breast cancer risk. Eur. J. Clin. Nutr. 2011, 65, 683–689.