May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Paracentral Visual Vield Loss in Glaucoma Patients Is Associated With the p53 Codon 72 Pro/Pro Genotype
Author Affiliations & Notes
  • D. R. Figueiredo Sena
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • L. R. Pasquale
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • A. W. Hewitt
    Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, Australia
  • J. E. Craig
    Ophthalmology, Flinders Medical Centre, Flinders University, Adelaide, Australia
  • C. O'Brien
    Ophthalmology, University College, Dublin, Ireland
  • A. Realini
    Ophthalmology, W. Va. Univ. Eye Inst., Morgantown, West Virginia
  • J. Haines
    Center for Human Genetics Research, Vanderbilt School of Medicine, Nashville, Tennessee
  • D. A. Mackey
    Ophthalmology, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia
  • J. L. Wiggs
    Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships D.R. Figueiredo Sena, None; L.R. Pasquale, None; A.W. Hewitt, None; J.E. Craig, None; C. O'Brien, None; A. Realini, None; J. Haines, None; D.A. Mackey, Pfizer Australia, F; J.L. Wiggs, None.
  • Footnotes
    Support NIH Grants EY015872, P30EY014104
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5605. doi:
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      D. R. Figueiredo Sena, L. R. Pasquale, A. W. Hewitt, J. E. Craig, C. O'Brien, A. Realini, J. Haines, D. A. Mackey, J. L. Wiggs; Paracentral Visual Vield Loss in Glaucoma Patients Is Associated With the p53 Codon 72 Pro/Pro Genotype. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5605.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose:: Ganglion cell death in glaucoma is associated with apoptosis. Many proteins participate in regulating apoptosis, including p53. Altered expression of p53 in lymphocytes from patients with normal tension glaucoma (NTG) has been demonstrated, however, previous gene association studies of p53 variants and glaucoma have been inconclusive. The purpose of this study is to determine the distribution of genotypes of a functional p53 polymorphism (codon 72 Pro/Arg) in patients with primary open angle glaucoma (POAG) and NTG.

Methods:: 533 adult onset POAG patients (290 Massachusetts Eye and Ear Infirmary and 243 from Glaucoma Inheritance Study in Tasmania, Australia), 88 NTG patients, and 106 control individuals were used for this study. POAG was defined as age of diagnosis greater than 35, intraocular pressure (IOP) >22 mm Hg, glaucomatous optic nerve damage, and visual field loss. NTG patients had evidence of optic nerve disease and visual field defects with IOP < 22 mm Hg. Automated Humphrey visual fields were scored by calculating the average pattern deviation in each of 6 regions corresponding to inferior and superior paracentral scotomas, inferior and superior nasal depressions and inferior and superior nasal step zones. p53 exon 4 was amplified and sequenced in all patients.

Results:: The Pro/Pro genotype was found in 53/533(10%) of POAG patients, 14/88(16%) of NTG patients, and 8/106(8%) of controls (p<.05 for NTG). In both POAG and NTG patients with reliable early visual field defects an increased frequency of the Pro/Pro genotyope was found in patients with paracentral scotomas 27/110(25%) compared with those with arcuate scotomas or nasal steps as the initial visual field defect 22/368(6%) (p=2.37x 10-7, chi square). For NTG and POAG patients with the Pro/Pro genotype the unadjusted relative risk of developing paracentral scotomas as an initial visual field defect.was 4.12 [2.44-6.93].

Conclusions:: These results show a significant difference in the distribution of alleles at the p53 codon 72 polymorphism in NTG and POAG patients with paracentral scotomas compared with arcuate scotomas and nasal steps.

Keywords: genetics • gene mapping • ganglion cells 

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