Abstract
Purpose
To investigate the association between VEGF gene polymorphism and age-related macular degeneration (AMD) in a Brazilian cohort.
Methods
We examined 160 affected individuals and 140 sex- and age-matched controls recruited at the Vision Institute and the Retina Department, São Geraldo Hospital, Minas Gerais Federal University, Brazil, between 2007 and 2011. Genotyping for the VEGF rs1413711 single nucleotide polymorphism (SNP) (+674C>T) was performed. The incidence rate ratios and 95% confidence interval (CI) for AMD for this genotype was calculated. The odds ratio (OR) was also assessed by using logistic regression, controlling for CFH and LOC387715 risk genotype.
Results
We observed a prevalence of homozygosity (TT genotype) of 18.1% for rs1413711 among AMD cases compared with 5.8% among controls (P < 0.002). The ORs for this polymorphism were 3.6 (95%CI 1.6–8.2) for homozygous subjects and 1.5 (95%CI 1.1–2.1, P < 0.01) if the subject had at least one risk allele. When we studied separately exudative and dry AMD groups, this polymorphism was statistically significant for both groups. Controlling for CFH and LOC387715 risk genotype the OR was 3.0 for VEGF homozygous, and the OR increases if the patient is homozygous for the three genes.
Conclusion
The present data suggests that VEGF TT genotype is associated with AMD among Brazilian patients.
Similar content being viewed by others
References
Seddon JM, Chen CA (2006) Epidemiology of age-related macular degeneration. In: Ryan SJ (ed) Retina. Elsevier, California, pp 1017–1025
Reynolds R, Hartnett ME, Atkinson JP, Giclas PC, Rosner B, Seddon JM (2009) Plasma complement components and activation fragments: associations with age-related macular degeneration genotypes and phenotypes. Invest Ophthalmol Vis Sci 50:5818–5827
Seddon JM, Reynolds R, Maller J, Fagerness JA, Daly MJ, Rosner B (2009) Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci 50:2044–2053
Almeida LNF, Carolino RM, Sperandio DC, Nehemy MB, De Marco LA (2009) The role of molecular genetic factors in age-related macular degeneration. Arq Bras Oftalmol 72:567–572
Hecker LA, Edwards AO, Ryu E, Tosakulwong N, Baratz KH, Brown WL, Charbel Issa P, Scholl HP, Pollok-Kopp B, Schmid-Kubista KE, Bailey KR, Oppermann M (2010) Genetic control of the alternative pathway of complement in humans and age-related macular degeneration. Hum Mol Genet 19:209–215
Lee AY, Kulkarni M, Fang AM, Edelstein S, Osborn MP, Brantley MA (2010) The effect of genetic variants in SERPING1 on the risk of neovascular age-related macular degeneration. Br J Ophthalmol 94:915–917
Schaumberg DA, Hankinson SE, Guo Q, Rimm E, Hunter DJ (2007) A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. Arch Ophthalmol 125:55–62
Wang G, Spencer KL, Court BL, Olson LM, Scott WK, Haines JL, Pericak-Vance MA (2009) Localization of age-related macular degeneration-associated ARMS2 in cytosol, not mitochondria. Invest Ophthalmol Vis Sci 50:3084–3090
Jiang H, Qu Y, Dang G, Zhang X, Yin N, Zhang Y, Bi H, Pan X, Xu X, Zhou F, Dai H (2009) Analyses of single nucleotide polymorphism and haplotype linkage of LOC387715 and the HTRA1 gene in exudative age-related macular degeneration in a Chinese cohort. Retina 29:974–979
Haines JL, Schnetz-Boutaud N, Schmidt S, Scott WK, Agarwal A, Postel EA, Olson L, Kenealy SJ, Hauser M, Gilbert JR, Pericak-Vance MA (2006) Functional candidate genes in age-related macular degeneration: significant association with VEGF, VDRLR, and LRP6. Invest Ophthalmol Vis Sci 47:329–335
Churchill AJ, Carter JG, Ramsden C, Turner SJ, Yeung A, Brenchley PE, Ray DW (2006) VEGF polymorphisms are associated with neovascular age-related macular degeneration. Hum Mol Genet 15:2955–2961
Janik-Papis K, Zaras M, Krzyzanowska A, Wozniak K, Blasiak J, Szaflik J, Szaflik JP (2009) Association between vascular endothelial growth factor gene polymorphisms and age-related macular degeneration in a Polish population. Exp Mol Pathol 87:234–238
Richardson AJ, Islam FM, Guymer RH, Cain M, Baird PN (2007) A tag-single nucleotide polymorphisms approach to the vascular endothelial growth factor-A gene in age-related macular degeneration. Mol Vis 26:2148–2152
Boekhoorn SS, Isaacs A, Uitterlinden AG, van Duijn CM, Hofman A, de Jong PT, Vingerling JR (2008) Polymorphisms in the vascular endothelial growth factor gene and risk of age-related macular degeneration: the Rotterdam Study. Ophthalmology 115:1899–1903
Qiu Y, Hoareau-Aveilla C, Oltean S, Harper SJ, Bates DO (2009) The anti-angiogenic isoforms of VEGF in health and disease. Biochem Soc Trans 37:1207–1213
Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME (2008) Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 27:331–371
Frank RN (1997) Growth factors in age-related macular degeneration: pathogenic and therapeutic implications. Ophthalmic Res 29:341–353
Eyetech Study Group (2003) Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology 110:979–986
Seddon JM, Sharma S, Adelman RA (2006) Evaluation of clinical age-related maculopathy staging system. Ophthalmology 113:260–266
Lin JM, Wan L, Tsai YY, Lin HJ, Tsai Y, Lee CC, Tsai CH, Tseng SH, Tsai FJ (2008) Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration. Am J Ophthalmol 145:1045–1051
Galan A, Ferlin A, Caretti L, Buson G, Sato G, Frigo AC, Foresta C (2010) Association of age-related macular degeneration with polymorphisms in vascular endothelial growth factor and its receptor. Ophthalmology 117:1769–1774
Fang AM, Lee AY, Kulkarni M, Osborn MP, Brantley MA Jr (2009) Polymorphisms in the VEGFA and VEGFR-2 genes and neovascular age-related macular degeneration. Mol Vis 10:2710–2719
Pugh CW, Ratcliffe P (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9:677–684
Harper SJ, Bates DO (2008) VEGF-A splicing: the key to anti-angiogenic therapeutics? Nat Rev Cancer 8:880–887
Acknowledgements
Supported in part by grants from CNPq, INCT in Molecular Medicine and FAPEMIG, Brazil.
Conflicts of interest
The authors have no financial or competing interests to declare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Almeida, L.N., Melilo-Carolino, R., Veloso, C.E. et al. Homozygosity for the +674C>T polymorphism on VEGF gene is associated with age-related macular degeneration in a Brazilian cohort. Graefes Arch Clin Exp Ophthalmol 250, 185–189 (2012). https://doi.org/10.1007/s00417-011-1807-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00417-011-1807-5