Association of Gene Polymorphisms With Primary Open Angle Glaucoma: A Systematic Review and Meta-Analysis

Abstract

for genetic studies of POAG. All case control studies investigating the association between singlenucleotide polymorphisms (SNPs) and POAG risk were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by fixed-or random-effect model. RESULTS. This meta-analysis included 108 case control studies involving 35,389 POAG patients and 51,742 controls. The pooled results showed a significant association between 20 SNPs in 12 genes (148Asp/Glu in APE1 gene; rs449647 in APOE gene; rs1052990 and rs4236601 in CAV1/CAV2 gene; rs1799750 in MMP gene; c.603T3A (Met98Lys) in OPTN gene; rs7081455 in PLXDC2 gene; rs1279683 in SLC23A2 gene; 372 T/C in TIMP1 gene; rs1927911, rs2149356, rs4986791, rs7037117, and rs10759930 in TLR4 gene; rs4656461 in TMCO1 gene; 399Arg/Gln in XRCC1 gene; and rs540782, rs547984, and rs693421 in ZP4 gene) with POAG. CONCLUSIONS. Based on the current meta-analysis, we indicate 20 SNPs in 12 genes (APE1, APOE, CAV1/CAV2, MMP, OPTN, PLXDC2, SLC23A2, TIMP1, TLR4, TMCO1, XRCC1, ZP4) as predictive risk factors for POAG. More studies with large sample sizes and various ethnicities are warranted in the future to provide more powerful evidence.

Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4

“…61 We speculate that the strength of association noted between APOE ε4 and POAG will depend on the proportion of NTG patients enrolled in a given study, which may explain some of the variability in the published individual studies [33][34][35][36][37][38][39][40][41][42] and meta-analyses. [43][44][45][46][47] What is the mechanism by which APOE ε4 may be protective in glaucoma? APOE is expressed in a variety of cell types in the healthy retina and the optic nerve, including Müller glia and astrocytes.…”

“…[33][34][35][36][37][38][39][40][41][42] Several meta-analyses found no association between APOE and glaucoma, 43,44 while others reported an association between the APOE ε4/ε4 genotype and POAG in Asians. 45,46 Another large meta-analysis reported an association between a single-nucleotide polymorphism (SNP) in the promoter region of APOE (rs449647) and glaucoma 47 ; this SNP, however, is not associated with AD. 48 Interestingly, APOE ε4 is associated with decreased risk for another common neurodegenerative disease of the eye, age-related macular degeneration (AMD), [49][50][51][52] opposite of its effect on AD.…”

Primary Open Angle Glaucoma and Vascular Risk Factors: A Review of Population Based Studies from 1990 to 2019

“…Several studies have revealed a significant role of the myocilin, optineurin, and cytochrome CYP1B1 genes in glaucoma development [13][14][15][16]. Moreover, genome-wide association studies have shown associations of sequence variants [17][18][19][20][21] and single-nucleotide polymorphisms [22][23][24][25][26] with POAG. Notwithstanding the role of genetic mutations and variations on glaucoma onset, the role of different systemic risk factors remains debatable.…”

Dataset of allele and genotype frequencies of the three functionally significant polymorphisms of the MMP genes in Russian patients with primary open-angle glaucoma, essential hypertension and peptic ulcer

“…The dataset contains the raw data (supplementary Table), frequencies of alleles and genotypes ( Table 1 ) for three SNPs of two MMP genes (rs1799750 MMP1 , rs3918242 and rs17576 MMP9 ) in Russian patients diagnosed with POAG, EH, and PU. These polymorphisms were previously reported for their association with POAG, EH, and PU ( Table 2 ) [1] , [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] . The studied SNPs manifest the regulatory potential ( Table 3 ), which is evidenced by several eQTLs ( Table 4 ) and splicing QTLs ( Table 5 ).…”