Purpose: To offer a comprehensive evaluation of the potential associations of TP53 polymorphisms with primary open-angle glaucoma (POAG) through a systematic review and meta-analysis of candidate genetic association study.
Methods: Medline, Embase, Science Citation Index, the Cochrane Library, and other databases (up to January 20, 2012) were searched by two investigators independently. Pooled odd ratios (ORs) and 95% confidence interval (CI) were used to assess the strength of the associations between two TP53 polymorphisms (codon 72 in exon 4 and 16 base-pair [bp] insertion in intron 3) and POAG. Statistical analysis was performed with a commercial statistical and data analysis software package.
Results: Nine independent studies on TP codon 72 (1930 cases and 1463 controls) and four articles on TP intron 3 16-bp insertion (858 cases and 683 controls) were identified. The overall results showed that there was significant association between TP53 codon 72 genotype and 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 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 POAG in Asian populations (recessive model: OR = 1.36, 95% CI 1.03-1.80, P = 0.026) but not in Caucasian populations. However, no significant finding was noted between P53Arg72Pro and risk for open-angle glaucoma either in high tension glaucoma or in normal tension glaucoma. Because of insufficient studies on TP53 16-bp 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 versus CG+GG) and intron 3 16-bp insertion (Ins versus Del) polymorphisms may affect individual susceptibility to POAG. Moreover, stratified analyses that detected the effect of TP53 codon 72 polymorphism seemed to be varied by ethnicity. Given the limited sample size, further investigations are needed to validate the association.