Association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and age-related macular degeneration

Age-Related Macular Degeneration (AMD) is an eye disease that results in progressive and irreversible loss of central vision and is considered as the primary cause of visual impairment, including blindness, in the elderly in industrialized countries. Oxidative stress has been implicated in the pathogenesis of AMD. The hOGG1 and the MUTYH genes play an important role in the repair of oxidatively damaged DNA in the base excision repair pathway. The DNA glycosylases encoded by the hOGG1 and MUTYH genes initiate this pathway by recognizing and removing 8-oxoguanine and adenine paired with 8-oxoguanine, respectively. Our study was designed to examine the association between the c.977C>G polymorphism (rs1052133) of the hOGG1 gene and the c.972G>C polymorphism (rs3219489) of the MUTYH gene and AMD as well as the modulation of this association by some clinical and lifestyle factors. Genotypes were determined in DNA from blood of 271 AMD patients, including 101 with wet and 170 with dry form of the disease and 105 sex- and age-matched individuals without AMD. We observed an association between AMD, dry and wet forms of AMD and the C/G genotype and the G allele of the c.977C>G-hOGG1 polymorphism (p 0.006; 0.009; 0.021 and 0.004; 0.005; 0.016 respectively). On the other hand, the C/C genotype and the C allele reduced the risk of AMD as well as of its dry form or wet form (p 0.002; 0.003; 0.010 and 0.004; 0.005; 0.016, respectively). Therefore, the associations we detected were driven by the dry AMD. We observed some statistically significant association between the occurrence of AMD and its dry and wet forms and genotypes of the other polymorphism, the c.972G>C-MUTYH polymorphism, but due to borderline character of all this association we do not consider them as medically relevant. Our findings suggest that the c.977C>G-hOGG1 polymorphism may be associated with dry AMD. Further studies are needed to determine possible association between AMD and the c.972G>C-MUTYH polymorphism.

► We checked for an association between the c.977G>C-hOGG1 and the c.972C>G-MUTYH polymorphisms and AMD risk.
► Genotypes were determined in DNA from blood of 271 AMD patients and 105 sex- and age-matched individuals without AMD.
► The presence of the C/G genotype and the G allele of the c.977C>G-hOGG1 polymorphism increased the risk of AMD.
► The occurrence of AMD was correlated with the presence of the C allele of the c.972G>C-MUTYH polymorphism.
► Our findings suggest that the c.977C>G-hOGG1 and c.972G>C-MUTYH polymorphisms may be associated with both dry and wet AMD.