Department of Medical Biological Disciplines, 64903Belgorod State University, Belgorod, Russia.
Department of Life Sciences, College of Science and General Studies, 101686Alfaisal University, Riyadh, Saudi Arabia.
Eur J Ophthalmol. 2022 Nov;32(6):3208-3219. doi: 10.1177/11206721221083722. Epub 2022 Mar 7.
The aim of this study was to investigate the role of functionally significant loci of the matrix metalloproteinases genes 1, 3, 9 ( and ) in the development of primary open-angle glaucoma (POAG) in Caucasians of the Central region of Russia.
In total 604 participants were recruited for the study, including 208 patients with POAG and 396 healthy controls. They were genotyped at eight single nucleotide polymorphisms (SNPs) of the three genes. The association was analyzed using logistic and log-linear regression. POAG-associated loci and their proxies were assessed for their functional prediction.
Variant allele Grs2250889 of was significantly associated with higher risk of POAG (OR = 1.57-1.71). Haplotype CCA [rs3918242-rs3918249-rs17576] of the gene was associated with lower risk of POAG (OR = 0.33). Allele Аrs3787268 of was associated with the low intraocular pressure in the POAG patients (β = -0.176 - -0.272), and so were haplotypes AA [rs17576-rs3787268] (β = -0.577) and AAC [rs17576-rs3787268- rs2250889] (β = -0.742) of the same gene, whereas allele 2G*rs1799750 of was associated with the earlier onset of the disease (β = -0.112 - -0.218). analysis of the polymorphisms suggested the functionality of POAG-associated SNPs and their proxies (epigenetic potential, expression and alternative splicing effects for several genes).
The gene polymorphisms are associated with POAG and intraocular pressure in POAG patients; rs1799750 of was associated with the earlier age of manifestation of the disease symptoms.
本研究旨在探讨基质金属蛋白酶基因 1、3、9（和）的功能显著位点在俄罗斯中部白种人原发性开角型青光眼（POAG）发病机制中的作用。
共纳入 604 名研究对象，包括 208 名 POAG 患者和 396 名健康对照者。对这 3 个基因的 8 个单核苷酸多态性（SNP）进行基因分型。采用逻辑和对数线性回归分析进行关联分析。对与 POAG 相关的基因座及其近等位基因进行功能预测评估。
等位基因 Grs2250889 与 POAG 风险增加显著相关（OR=1.57-1.71）。基因的 CCA[rs3918242-rs3918249-rs17576]单倍型与 POAG 低风险相关（OR=0.33）。等位基因 Ars3787268 与 POAG 患者的低眼压相关（β=-0.176-0.272），基因的 rs17576-rs3787268 单倍型（β=-0.577）和 rs17576-rs3787268-rs2250889 单倍型（β=-0.742）也与 POAG 患者的低眼压相关，而基因的 2G*rs1799750 等位基因与疾病发病年龄较早相关（β=-0.112-0.218）。对多态性的分析提示与 POAG 相关的 SNP 及其近等位基因具有功能（几个基因的表观遗传潜力、表达和可变剪接效应）。
基因多态性与 POAG 和 POAG 患者的眼压相关，基因的 rs1799750 与疾病症状出现年龄较早相关。
