The p53 codon 72 PRO/PRO genotype may be associated with initial central visual field defects in caucasians with primary open angle glaucoma.
BACKGROUND
Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg) and the subset of primary open angle glaucoma (POAG) patients with early loss of central visual field.


METHODS
Genotypes for the p53 codon 72 polymorphism (Pro/Arg) were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST). The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral). All cases and controls were Caucasian with European ancestry.


RESULTS
The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p=2.7 × 10(-5)). We replicated this finding in the GIST cohort (p  =7.3 × 10(-3), and in the pooled sample (p=6.6 × 10(-7)) and in a meta-analysis of both the US and GIST datasets (1.3 × 10(-6), OR 2.17 (1.58-2.98 for the PRO allele).


CONCLUSIONS
These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients.
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. janey_wiggs@meei.harvard.edu
Janey L
JL
Wiggs
Alex W
AW
Hewitt
Bao Jian
BJ
Fan
Dan Yi
DY
Wang
Dayse R
DR
Figueiredo Sena
Colm
C
O'Brien
Anthony
A
Realini
Jamie E
JE
Craig
David P
DP
Dimasi
David A
DA
Mackey
Jonathan L
JL
Haines
Louis R
LR
Pasquale
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D016022:Case-Control Studies; D003062:Codon; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000235:genetics*; D012607:Scotoma / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014794:Visual Fields; D044465:White People / Q000235:genetics
D003062:Codon; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011392:Proline