Korean J Ophthalmol.  2012 Dec;26(6):423-427. 10.3341/kjo.2012.26.6.423.

Association between Exudative Age-related Macular Degeneration and the G6721T Polymorphism of XRCC7 in Outdoor Subjects

• Saadat I
• Vakili-Ghartavol R
• Farvardin-Jahromi M
• Saadat M

• KMID: 1499679
• DOI: http://doi.org/10.3341/kjo.2012.26.6.423

Abstract

PURPOSE
To investigate whether the G6721T polymorphism (rs.7003908) of the non-homologous end-joining DNA repair XRCC7 gene contributes to the development of exudative age-related macular degeneration (ARMD).
METHODS
The present case-control study consisted of 111 patients with exudative ARMD and 112 sex frequency-matched healthy controls that were randomly selected from unrelated volunteers in the same clinic. Genotypes were determined by the Restriction Fragment Length Polymorphism (PCR-RFLP) based method. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ARMD risk associated with polymorphism of XRCC7. In all analysis the GG genotype was considered to be the reference genotype.
RESULTS
There was no significant association between genotypes of XRCC7 and susceptibility to ARMD. Considering the significant difference in age distribution between cases and controls, age was used as a covariate in further analysis. After ORs were adjusted for age, the same result was observed. In the next step we stratified our subjects into outdoor and indoor groups according to their job titles. The outdoor and indoor patients were occupationally exposed to sunlight and not exposed to sunlight, respectively. Our present study showed that among indoor subjects there was no association between XRCC7 polymorphism and susceptibility to ARMD. However, among outdoor subjects, the GT + TT genotypes compared to the GG genotype increased the risk of ARMD (OR, 3.13; 95% CI, 1.04-9.39; p = 0.042).
CONCLUSIONS
Our study revealed that the T allele of the G6721T polymorphism of XRCC7 increased the risk of ARMD among outdoor subjects.

Keyword

Macular degeneration; Susceptibility; XRCC7

MeSH Terms

Aged
DNA/*genetics
DNA-Activated Protein Kinase/*genetics/metabolism
*Environmental Exposure
Exudates and Transudates
Female
Follow-Up Studies
*Genetic Predisposition to Disease
Genotype
Humans
Macular Degeneration/*genetics/metabolism
Male
Middle Aged
Nuclear Proteins/*genetics/metabolism
Polymerase Chain Reaction
*Polymorphism, Genetic
Retrospective Studies
Risk Factors
Nuclear Proteins
DNA
DNA-Activated Protein Kinase

Reference

1. Klaver CC, Wolfs RC, Assink JJ, et al. Genetic risk of age-related maculopathy: population-based familial aggregation study. Arch Ophthalmol. 1998. 116:1646–1651.

2. Klein BE, Klein R, Lee KE, et al. Risk of incident age-related eye diseases in people with an affected sibling: the Beaver Dam Eye Study. Am J Epidemiol. 2001. 154:207–211.

3. De Jong PT, Klaver CC, Wolfs RC, et al. Familial aggregation of age-related maculopathy. Am J Ophthalmol. 1997. 124:862–863.

4. Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related maculopathy. Am J Ophthalmol. 1997. 123:199–206.

5. Seddon JM, Willett WC, Speizer FE, Hankinson SE. A prospective study of cigarette smoking and age-related macular degeneration in women. JAMA. 1996. 276:1141–1146.

6. Plestina-Borjan I, Klinger-Lasic M. Long-term exposure to solar ultraviolet radiation as a risk factor for age-related macular degeneration. Coll Antropol. 2007. 31:Suppl 1. 33–38.

7. Chalam KV, Khetpal V, Rusovici R, Balaiya S. A review: role of ultraviolet radiation in age-related macular degeneration. Eye Contact Lens. 2011. 37:225–232.

8. Roberts JE. Ultraviolet radiation as a risk factor for cataract and macular degeneration. Eye Contact Lens. 2011. 37:246–249.

9. Szaflik JP, Janik-Papis K, Synowiec E, et al. DNA damage and repair in age-related macular degeneration. Mutat Res. 2009. 669:169–176.

10. Seddon JM, Santangelo SL, Book K, et al. A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions. Am J Hum Genet. 2003. 73:780–790.

11. Gottlieb TM, Jackson SP. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 1993. 72:131–142.

12. Hartley KO, Gell D, Smith GC, et al. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell. 1995. 82:849–856.

13. Ferguson DO, Sekiguchi JM, Chang S, et al. The nonhomologous end-joining pathway of DNA repair is required for genomic stability and the suppression of translocations. Proc Natl Acad Sci U S A. 2000. 97:6630–6633.

14. Singleton BK, Priestley A, Steingrimsdottir H, et al. Molecular and biochemical characterization of xrs mutants defective in Ku80. Mol Cell Biol. 1997. 17:1264–1273.

15. Jackson SP. DNA-dependent protein kinase. Int J Biochem Cell Biol. 1997. 29:935–938.

16. Sipley JD, Menninger JC, Hartley KO, et al. Gene for the catalytic subunit of the human DNA-activated protein kinase maps to the site of the XRCC7 gene on chromosome 8. Proc Natl Acad Sci U S A. 1995. 92:7515–7519.

17. Wang SY, Peng L, Li CP, et al. Genetic variants of the XRCC7 gene involved in DNA repair and risk of human bladder cancer. Int J Urol. 2008. 15:534–539.

18. Wang LE, Bondy ML, Shen H, et al. Polymorphisms of DNA repair genes and risk of glioma. Cancer Res. 2004. 64:5560–5563.

19. Hirata H, Hinoda Y, Matsuyama H, et al. Polymorphisms of DNA repair genes are associated with renal cell carcinoma. Biochem Biophys Res Commun. 2006. 342:1058–1062.

20. Hirata H, Hinoda Y, Tanaka Y, et al. Polymorphisms of DNA repair genes are risk factors for prostate cancer. Eur J Cancer. 2007. 43:231–237.

21. Liu Y, Zhang H, Zhou K, et al. Tagging SNPs in non-homologous end-joining pathway genes and risk of glioma. Carcinogenesis. 2007. 28:1906–1913.

22. Gangwar R, Ahirwar D, Mandhani A, Mittal RD. Do DNA repair genes OGG1, XRCC3 and XRCC7 have an impact on susceptibility to bladder cancer in the North Indian population? Mutat Res. 2009. 680:56–63.

23. Othman H, Gholampour AR, Saadat I, et al. Age-related macular degeneration and genetic polymorphisms of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1). Mol Biol Rep. 2012. 39:3299–3303.

24. Othman H, Saadat I, Farvardin-Jahromi M, Saadat M. Susceptibility to exudative age-related macular degeneration and three genetic polymorphisms of glutathione S-transferase Z1 (GSTZ1). Eur J Ophthalmol. 2012. 22:431–435.

25. Mohamadynejad P, Saadat M. Genetic polymorphisms of XRCC1 (at codons 194 and 399) in Shiraz population (Fars province, southern Iran). Mol Biol Rep. 2008. 35:669–672.

26. Rafiee L, Saadat I, Saadat M. Glutathione S-transferase genetic polymorphisms (GSTM1, GSTT1 and GSTO2) in three Iranian populations. Mol Biol Rep. 2010. 37:155–158.

27. Saadat M, Farvardin-Jahromi M. Occupational sunlight exposure, polymorphism of glutathione S-transferase M1, and senile cataract risk. Occup Environ Med. 2006. 63:503–504.