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S. Zareparsi, C. Daugherty, H. Curtis, B. Ninness, M. Offutt, J. Thurston, T. Realini, J. Charlton; Primary Open Angle Glaucoma Is Associated With Polymorphisms Within the P53 Gene. Invest. Ophthalmol. Vis. Sci. 2009;50(13):872.
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There have been inconsistent reports regarding increased risk of primary open-angle glaucoma (POAG) and a polymorphism (Arg72Pro) within the tumor suppressor gene, p53. While an association with increased risk of POAG was observed by two groups, this finding was not replicated by two other groups. Each study examined different ethnicities outside of the United States. We examined the association between POAG and p53 in a Caucasian population recruited at the West Virginia University Eye Institute.
Subjects were classified after a comprehensive ophthalmologic examination and blood samples were collected after obtaining informed consent. We generated genotypes in 200 POAG patients and 165 controls for the following polymorphisms within p53: rs1042522 (Arg72Pro), rs17878362 (16 bp Ins/Del), and rs1800371 (Pro47Ser) by PCR amplification followed with restriction digestion and sequence analysis.
There was a significant difference in genotypic frequencies for rs1042522 between POAG patients and controls (Χ2= 6.87, p=0.03). The frequency of the Arg allele was significantly increased in POAG patients compared to controls (p=0.02). Individuals who were homozygotes for the Arg allele have a 1.9-fold significantly increased risk of developing glaucoma (95%CI: 1.16-2.82, p=0.01). Moreover, there was a specific haplotype (rs1042522: Arg & rs17878362: Del) that was significantly more frequent among POAG cases than controls (0.79 vs. 0.68, p=0.02). The presence of the risk allele (Arg/Del) was associated with a 2.0-fold significant increased risk of developing glaucoma (95%CI: 1.19-2.55, p=0.01). Surprisingly, we found that the frequency of the Arg allele was even higher in the normal-tension glaucoma (NTG) subtype compared to high-tension POAG (0.81 vs. 0.76).
Our preliminary results indicate that a haplotype within p53 is associated with susceptibility to POAG. Further studies consisting of additional subjects and a more detailed analysis of genetic variations within p53 are warranted in order to determine its role in the pathogenesis of POAG.
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