Association between exudative age-related macular degeneration and the G6721T polymorphism of XRCC7 in outdoor subjects

Familial aggregation has been demonstrated for age-related macular degeneration (ARMD) [1-3] and it is likely that both genetic susceptibility [1-4] and environmental risk factors [5-9] play a role. A genome wide scan for ARMD provides evidence for linkage to potential loci on human chromosome 8 [10]. A relationship between long-term sunlight exposure and increased risk of ARMD has been suggested [6] and epidemiologic evidence indicates a trend toward association between severity of light exposure and ARMD [7,8]. Short wavelength radiation and blue light induce significant oxidative stress to the retinal pigment epithelium (RPE). ARMD results from damage to the RPE cells, which is mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. Therefore, individuals with impaired DNA repair may be more susceptible to ARMD [9]. Gene XRCC7 (MIM: 600899, GenBank accession no: {"type":"entrez-nucleotide","attrs":{"text":"NM_001469","term_id":"573014813","term_text":"NM_001469"}}NM_001469) encodes the catalytic subunit of a nuclear DNA-dependent serine/threonine protein kinase (DNA-PK). As the catalytic subunit of the DNA-PK complex, XRCC7 aids in the recognition and repair of DNA double-strand breaks (DSBs) [11]. DNA-PK activity is activated by binding to free DNA ends and it catalyzes the rejoining of DSB [12]. Thus, DNA-PK activity is essential for non-homologous end joining and V (D) J recombination. Deficiencies in DNA-PK activity are clinically significant. Mice with inactivated components of DNA-PK show severe combined immunodeficiency as well as ionizing radiation hypersensitivity [13,14]. Cells defective in DNA-PK components are hypersensitive to killing by ionizing radiation due to an inability to repair DSBs effectively [15]. The gene encoding XRCC7 is located on human chromosome 8q12 [16]. It has been suggested that the genetic G6721T polymorphism of human XRCC7 (rs.7003908), in intron 8, may regulate splicing and cause mRNA instability [16]. The association between the G6721T polymorphism of XRCC7 and cancers has been studied [17-22]. Additionally, human chromosome 8, where the gene encoding XRCC7 is located, has been associated with an increased risk of ARMD [10]. Since ARMD results from damage to RPE cells caused by oxidative stress and the G6721T polymorphism of XRCC7, may regulate splicing and cause mRNA instability [16], we hypothesize that XRCC7 polymorphism is associated with ARMD. To the best of our knowledge, there is no report on the association between XRCC7 polymorphism and ARMD.