title: Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population.
abstract: The pathogenesis of age-related macular degeneration (AMD) is thought to be determined by an array of environmental and genetic factors. The association of increased expression of vascular endothelial growth factor (VEGF) with AMD, especially the wet form of AMD, was reported in several studies. The VEGF gene is highly polymorphic and some of its polymorphisms may affect its expression. In our work, we searched for an association between the -460C> (rs833061) and -634G>C (rs2010963) polymorphisms of the VEGF gene and the occurrence of AMD and its dry and wet forms. We have chosen these polymorphisms because they were shown to be significant in other studies and we previously showed their association with diabetic retinopathy. A total of 401 individuals were enrolled in this study: 136 controls, and 88 patients with dry and 177 with wet AMD. The polymorphisms were determined with DNA from peripheral blood lymphocytes by allele-specific and restriction fragment length polymorphism polymerase chain reaction. The significance of the polymorphisms was assessed by multiple logistic regression, producing odds ratios (ORs) and 95% confidence intervals (CIs). We observed a weak association (OR 2.90) between AMD occurrence and the C/T genotype of the -460C>T polymorphism. An association (OR 3.77) between the C/T genotype of the -460C>T polymorphism and the occurrence of dry AMD was observed. The T/T genotype considerably lowered the risk of dry AMD (OR 0.19). Dry AMD was associated with the C/C genotype of the -634G>C polymorphism (OR 3.68). Another weak association (OR 2.63) was found between the C/T genotype of the -460C>T polymorphism and the occurrence of wet AMD. The occurrence of AMD was correlated with the presence of the combined C/T-G/G genotype of both polymorphisms (OR 2.41), whereas the T/T-G/G and T/T-G/C genotypes exerted a protective effect against the disease (OR 0.22 and 0.48, respectively). The presence of the C/T-G/G and C/T-C/C combined genotypes increased the risk of dry AMD (OR 2.08 and 3.77, respectively), whereas the presence of the T/T-G/G and T/T-G/C genotypes decreased the risk (OR 0.15 and 0.28, respectively). In the wet form of AMD, the combined genotype C/T-G/G slightly favored the disease (OR 2.61) and the T/T-G/G genotype had a protective effect (OR 0.25). Analysis of haplotypes of both polymorphisms yielded similar results for AMD in general as well as for the dry and wet forms of the disease: the CG haplotype favored both forms of AMD, whereas the TG haplotype protected against both forms of AMD. The results obtained indicate that the -460C>T and -634G>C polymorphisms of the VEGF gene may be associated with the dry and wet forms of AMD in a Polish population.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Janik-Papis
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zaras
authors.forename: Anna
authors.initials: A
authors.lastname: Krzyzanowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wozniak
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
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; D005260:Female; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011044:Poland; D011110:Polymorphism, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A