Evaluation of NOS3 polymorphisms in patients with primary open angle glaucoma

Abstract

Abstract: : Purpose:Defects in endothelial nitric oxide synthase (eNOS) activity may contribute to primary open angle glaucoma (POAG) by affecting the tone of the optic nerve vasculature and by affecting aqueous humor outflow. Molecular studies have shown that two polymorphisms of NOS3 (Asp298Glu and T –786 C) produce reduced eNOS activity, and the T –786C polymorphism has been previously reported to be associated with POAG. The purpose of this study is to determine the distribution of alleles at these polymorphic sites in patients affected by primary open angle glaucoma and in patients affected by normal tension glaucoma. Methods:110 patients affected with (POAG), 50 patients affected with low tension glaucoma (LTG), and 106 age, sex and ethnically matched controls were used for this study. POAG was defined as age of diagnosis greater than 35, intraocular pressure greater than 22 mm Hg in both eyes, glaucomatous optic nerve damage in both eyes, and visual field loss in at least one eye. Low tension patients had evidence of optic nerve disease and visual field defects with intraocular pressure less than 22 mm Hg. Three polymorphisms in the NOS3 gene were analyzed: T –786C (5’UTR), Asp298Glu (exon 7), and a VNTR in intron 4. Alleles at the T–786C and Asp298Glu polymorphisms were identified by sequencing after PCR amplification of genomic DNA. VNTR alleles were identified after polyacrylamide gel electrophoresis of the genomic DNA PCR amplification products. Results:For all three NOS3 polymorphisms, the distribution of alleles was not statistically different between the POAG population, the LTG population and the control population. However, in POAG and LTG patients where early visual field defects could be identified (N = 80), an increased frequency of the CC genotype of the T –786C polymorphism was found in patients with paracentral scotomas compared to patients without paracentral scotomas (36% and 6% respectively, p<0.001, chi–square). Conclusions:The results of this study indicate that the CC genotype of the T –786C polymorphism of the NOS3 gene is significantly more frequent in POAG or LTG patients with paracentral scotomas as their initial visual field defect. Although based on a limited number of patients, this study suggests that glaucoma patients who are NOS3–786CC are at a higher risk for developing early loss of central vision.

Keywords: genetics • visual fields • nitric oxide