PURPOSE To offer a comprehensive evaluation of the potential associations of TP53 polymorphisms with primary open angle glaucoma through a systematic review and meta-analysis of candidate genetic association study.
METHODS Medline, Embase, Science Citation Index, the Cochrane Library and other database (up to January 20, 2012) were searched by two investigators independently. Pooled odd ratios (ORs) and 95% confidence interval (CI) were employed to assess the strength of the associations between two TP53 polymorphisms (codon 72 in exon 4 and 16 base pair insertion in intron 3) and primary open angle glaucoma (POAG) .Statistical analysis was performed with STATA statistical software.
RESULTS  Nine independent studies on TP codon 72 (1930 cases and 1463 controls) and four articles on TP intron 3 16bp insertion (858 cases and 683 controls) were identified. The overall results showed that there was significant association between TP53 codon 72 genotype and primary open angle glaucoma(POAG) risk in the recessive model (OR=1.31 ,95% CI 1.05 -1.64, p = 0.017). Also, our analysis suggested that TP53 intron 3 16-bp insertion polymorphism was associated with decreased primary open angle glaucoma (POAG)  risk in overall population when examining the contrast of Ins versus Del (OR 0.75, 95% CI = 0.57-0.97,P = 0.031). In subgroup analyses for ethnicity (Caucasian, Asian), we detected the association between codon 72 polymorphism and risk for primary open angle glaucoma in Asian (Recessive model OR=1.36, 95% CI 1.03 -1.80, p = 0.026) but not in Caucasian. However, no significant finding was noted between P53Arg72Pro and risk for open angle glaucoma either in high tension glaucoma (HTG) or in normal tension glaucoma (NTG).Because of insufficient studies on TP53 16bp insertion polymorphism, No subgroup analyses were conducted according to ethnicity and glaucoma subtype to detect the effect of this polymorphism on the susceptibility to POAG.
CONCLUSIONS This meta-analysis showed the evidence that TP53 codon 72 (CC vs. CG+GG) and intron 3 16-bp insertion (Ins vs. Del) polymorphisms may affect individual susceptibility to primary open angle glaucoma. Moreover, stratified analyses detected the effect of TP53 codon 72 polymorphism seem to be varied by ethnicity. Given the limited sample size, further investigations are needed to validate the association.