title: Association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and age-related macular degeneration.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Synowiec
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zaras
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D057092:Geographic Atrophy / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D041623:Tomography, Optical Coherence; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000235:genetics*
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; C479058:oxoguanine glycosylase 1, human