Genetic variability in DNA repair proteins in age-related macular degeneration

Int J Mol Sci. 2012 Oct 18;13(10):13378-97. doi: 10.3390/ijms131013378.


The pathogenesis of age-related macular degeneration (AMD) is complex and involves interactions between environmental and genetic factors, with oxidative stress playing an important role inducing damage in biomolecules, including DNA. Therefore, genetic variability in the components of DNA repair systems may influence the ability of the cell to cope with oxidative stress and in this way contribute to the pathogenesis of AMD. However, few reports have been published on this subject so far. We demonstrated that the c.977C>G polymorphism (rs1052133) in the hOGG1 gene and the c.972G>C polymorphism (rs3219489) in the MUTYH gene, the products of which play important roles in the repair of oxidatively damaged DNA, might be associated with the risk of AMD. Oxidative stress may promote misincorporation of uracil into DNA, where it is targeted by several DNA glycosylases. We observed that the g.4235T>C (rs2337395) and c.-32A>G (rs3087404) polymorphisms in two genes encoding such glycosylases, UNG and SMUG1, respectively, could be associated with the occurrence of AMD. Polymorphisms in some other DNA repair genes, including XPD (ERCC2), XRCC1 and ERCC6 (CSB) have also been reported to be associated with AMD. These data confirm the importance of the cellular reaction to DNA damage, and this may be influenced by variability in DNA repair genes, in AMD pathogenesis.

Publication types

  • Review

MeSH terms

  • DNA Glycosylases / genetics*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Macular Degeneration / genetics
  • Macular Degeneration / pathology*
  • Polymorphism, Genetic
  • Uracil-DNA Glycosidase / genetics
  • Uracil-DNA Glycosidase / metabolism
  • Xeroderma Pigmentosum Group D Protein / genetics
  • Xeroderma Pigmentosum Group D Protein / metabolism


  • DNA-Binding Proteins
  • DNA Glycosylases
  • Uracil-DNA Glycosidase
  • Xeroderma Pigmentosum Group D Protein
  • DNA Repair Enzymes