Distribution of p53 codon 72 Polymorphism in Primary Open Angle and Low Tension Glaucoma

Abstract

Abstract: : Purpose: In glaucoma ganglion cell death is associated with apoptosis. p53 is one protein that regulates apoptosis. Previous studies have reported that the Arg/Arg genotype of the p53 gene codon 72 polymorphism is associated with an increased risk of cervical cancer and that the Pro/Pro form of the polymorphism is associated with primary open angle glaucoma. Altered expression of p53 in lymphocytes from patients with low tension glaucoma has also been demonstrated. The purpose of this study is to determine the distribution of the genotypes of the p53 codon 72 polymorphism in patients with primary open angle glaucoma and low tension glaucoma. Methods: 135 patients affected with adult onset primary open angle glaucoma (POAG), 24 patients affected with low tension glaucoma (LTG), and 106 age, sex and ethnically matched control individuals were used for this study. POAG was defined as IOP 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 optic nerve disease and visual field defects with IOP less than 22 mm Hg. A region of exon 4 of the p53 gene containing the polymorphic DNA sequence was amplified and sequenced in all patients using an ABI310 automated sequencer and BIGDYE sequencing chemistry. Results: The Pro/Pro genotype was found in 17/135 (13%) of POAG patients, 4/24 (17%) of LTG patients, and in 8/106 (8%) of controls. In the patients studied, the genotype distribution was in Hardy-Weinberg equilibrium (Pvalue>0.05, chi-square). The Pro/Pro genotype may be slightly more common in POAG patients of African-American descent (5/18, 28%). In POAG and LTG patients where early visual field defects could be identified, an increased frequency of central arcuate scotomas were found in patients with the Pro/Pro genotype (12/15 80%) compared with the Arg/Arg genotype (11/31 35% Pvalue<0.01). Conclusions: The results of this study did not demonstrate a significant difference in the distribution of alleles at the p53 codon 72 polymorphism in patients with POAG or LTG compared with a control population. These results suggest that patients with the Pro/Pro genotype may be more likely to develop central arcuate scotoma as initial visual field defects, however additional studies are necessary to confirm this association.

Keywords: genetics • ganglion cells • apoptosis/cell death