Distributions of p53 codon 72 polymorphism in primary open angle glaucoma. (Clinical Science).

Background: Glaucomatous neuropathy is a type of cell death by apoptosis. The p53 gene is one of the regulatory genes of apoptosis. Recently, p53 codon 72 polymorphism has been extensively studied to determine the risk factors responsible for many diseases. In the p53 gene, a single base change from G to C causes the alternation of amino acid residue 72 From arginine to proline. In this study the association between p53 codon 72 polymorphism and primary open angle glaucoma (POAG) patients was evaluated.

Methods: 58 POAG patients and 59 healthy volunteers were enrolled in this study. Polymerase chain reaction based analysis was used to resolve the p53 codon 72 polymorphism.

Results: There were significant differences in the distribution of the polymorphism between the control subjects and the POAG patients (p = 0.00782) The praline form of p53 gene codon 72 appears to be a significant risk factor in the development of POAG (odds ratio 2.389, 95% confidence interval: 1.14 to 5.01).

Conclusions: Retinal ganglion cells die during POAG by apoptosis. The tumour suppressor protein, p53, is one of the primary regulators steps of apoptosis, and the results of our study are compatible with this concept.

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Glaucoma is a complex disease. Both mechanical and vascular hypotheses have been proposed as the mechanism. Regardless of the mechanism, the ganglion cells ultimately die, which represents the final common pathway of glaucomatous vision loss. (1 2) The major risk factors for open angle glaucoma include the level of intraocular pressure (IOP), ethnicity, some aspects of vascular function, high refractive errors, and a family history of glaucoma? Those with a first degree relative with glaucoma have up to four times the risk of developing the disease. At least one gene, located on chromosome lq, is known to be associated with a form of open angle glaucoma. (4) It is likely that several candidate genes influencing glaucoma will be detected. Nevertheless, there are many people with IOP above the statistically normal range who suffer no clinical damage in their lifetimes. Others have glaucoma within the normal IOP range. Hence, IOP level is not used in the definition of glaucoma. TOP is simply a risk factor for gl aucoma and is not the only mechanism causing ganglion cell loss in glaucoma. Rather, elevated IOP damages ganglion cells that have a genetic susceptibility to this form of stress. (5 6)

Several studies demonstrated that retinal ganglion cells die during development and as a result of a variety of optic nerve diseases by a form of cell death known as apoptosis. (3-6) Apoptosis is a genetically controlled form of cell death. This mechanism of cell death is controlled by specific genes and their products that are activated by the dying cell. (7-11) One of the primary regulatory steps of apoptosis is the activation of the tumour suppressor protein, p53. p53 is one of the major guardians of the genome, and can arrest the cell cycle in response to DNA damage or direct the damaged cell to an apoptotic pathway. Cell cycle arrest can be …