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D.R. Figueiredo Sena, L. Pasquale, C. O'Brien, A. Realini, R. Allingham, M.A. Hauser, M.A. Pericak–Vance, E. DelBono, J.L. Haines, J.L. Wiggs; Distribution of NOS3 and P53 Genotypes in Glaucoma Patients After Stratification by Initial Visual Field Defect . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1094.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Primary open angle glaucoma (POAG) is a complex inherited disease caused by multiple genetic factors. One approach to identify genes that contribute to complex disorders is to stratify the complex phenotype using endophenotypes defined by specific clinical parameters. In this study we have stratified a population of POAG patients according to the location of the initial visual field defect. To identify associated genetic factors we have examined the distribution of alleles at polymorphic sites in two genes likely to contribute to retinal ganglion cell loss: endothelial nitric oxide synthase (NOS3) and p53. Methods: POAG was defined as intraocular pressure greater than 22 mm Hg in both eyes and glaucomatous optic nerve damage and visual field loss in at least one eye. Humphrey automated visual fields demonstrating the earliest reproducible defects were selected for each patient. Average pattern deviations in each of 6 regions of the visual field were calculated. The T –786C (5’UTR) NOS3 and the p53 Pro72Arg polymorphisms were selected for this study. Alleles were identified by sequencing after PCR amplification of genomic DNA. Results: Initial visual field defects were identified in 166 patients (63 paracentral scotomas and 103 nasal step/arcuate scotomas). The CC genotype of the NOS3 T –786C polymorphism was found in 20/63 patients with paracentral scotomas and 2/97 patients with nasal step/arcuate scotomas (p < .001). The Pro/Pro genotype of the p53 Pro72Arg polymorphism was also more frequent in patients with paracentral scotomas (18/57) compared with patients with nasal step/arcurate scotomas (6/103) (p < .001). 4 of the paracentral scotoma patients had both the T –786C CC genotype and the Pro72Arg Pro/Pro genotype. Conclusions: The results of this study indicate that the NOS3 T –786C CC genotype and the p53 Pro72Arg Pro/Pro genotype are more frequent in glaucoma patients with paracentral scotomas as their initial visual field defect. Interestingly, these genes appear to be independently associated with this endophenotype. Although based on a limited number of patients, this study suggests that glaucoma patients who are NOS3 T –786C CC or p53 Pro72Arg Pro/Pro are at a higher risk for developing early loss of central vision.
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