Associations of polymorphisms of rs1015213 with primary angle closure glaucoma-recent evidence and a meta-analysis

Background: Primary angle closure glaucoma (PACG) has been thought to have a significantly genetic basis for a long time, and genome-wide association studies (GWAS) have identified various candidate genes including PCMTD1-ST18 rs1015213 as susceptibility loci. However, different results produced inconsistent results and make the conclusions controversial in some extent. Thus, we carried out a systematic review, attempting to summarize the recent evidence and determine the association of rs1015213 with PACG risk.

Methods: A systematic literature search was conducted to identify all published studies on associations of rs1015213 (PCMTD1-ST18) polymorphism and PACG risk up to April 30, 2015. Selection of eligible studies was undertaken by two investigators according to inclusion criteria. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as the pooled ocular biometric measures in different genotype or allele groups, were collected and analyzed. Heterogeneity was measured using the chi-square-based Q statistic test and I(2) metric. Publication bias of the included articles was evaluated using funnel plots.

Results: 21 eligible studies were included, among them 15 studies with enough data to estimate OR were included for meta-analysis, with a total of 24764 subjects (4737 PACG patients and 20027 controls), including 19416 Asian subjects (4378 PACG patients and 15038 controls) and 5348 Caucasian subjects (359 PACG patients and 4989 controls). Low heterogeneity was detected among studies (for Asian subgroups P=0.80, I(2)=0%, for Caucasian subgroups P=0.78, I(2)=0%, for all groups, P=0.89, I(2)=0%), thus, only fixed-effects model was used in the meta-analysis. The results showed that the frequencies of the TT genotype of rs1015213 were significant higher in PACG group than the controls in Asians (OR=1.51, 95% CI 1.27-1.79, P<0.01) but not in Caucasians (OR=1.54, 95% CI 0.94-2.54, P=0.09). In sensitivity analysis the significance of the pooled OR remained almost the same when removing studies individually. Visual inspection of the funnel plots revealed no asymmetry. 6 studies were included for evaluating the association between rs1015213 polymorphism with axial length (AL) and anterior chamber depth (ACD), all of them showed that rs1015213 polymorphism is independent with AL (Shi, P=0.528; Day, P=0.74; Nongpiur, pooled P=0.067, respectively). 5 studies showed that rs1015213 polymorphism was significantly associated with a shallow ACD (P<0.05) but the other study did not support this result.

Conclusion: Our meta-analysis suggests that rs1015213 (TT genotype) is associated with PACG in Asian populations, but this association is not significant in Caucasian population and need more data. Some literatures also supported that rs1015213 polymorphism was associated with a shallow ACD but not with a short AL, however the evidences are not sufficient yet.