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Fangyao Tang, Shisong Rong, Li Ma, Chi Pui Pang, Clement C Y Tham, Li Jia Chen; Genetic Associations of Primary Angle Closure Glaucoma: A Systematic Review and Meta-analysis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2548.
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To summarize the reported gene variants and determine their associations with primary angle closure glaucoma (PACG), primary angle closure (PAC) and primary angle closure suspect (PACS).
Literature search for genetic association studies of PACG, PAC and/or PACS published between year 1946 and August 25, 2014 was done in the MEDLINE, EMBASE and Cochrane Library databases, along with manual search in the reference lists of the included reports. Odds ratio (OR) and 95% confidence intervals (CI) for each gene variant were estimated using the random-effect model if I2 ≥50%, otherwise the fixed-effect model was used. The R software was used for statistical analyses.
A total of 30 articles were identified, involving more than 40 genes/loci and over 150 genetic variants. Among them, 27 studies that provided sufficient genotypic data were included for meta-analysis. We found gene loci that were identified by genome-wide association studies (GWAS) were successfully replicated in follow-up studies, including PLEKHA7 (rs11024102, p=0.0002, OR=1.25, I2=0), COL11A1 (rs3753841, p=0.0007, OR=1.23, I2=0), and PCMTD1/ST18 (rs1015213, p=0.022, OR=1.59, I2=21%). Moreover, a candidate gene MMP9 (rs3918249, p=0.027, OR=1.51, I2=0) was associated with PACG. Sensitivity analysis confirmed the associations. In contrast, we did not find any gene variants that were associated specifically with PAC or PACS.
Our results confirmed the associations of SNPs in PLEKHA7, COL11A1 and PCMTD1/ST18 with PACG and identified a borderline association of MMP9 with PACG. These genes should thus be taken for biological studies in PACG.
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