Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Am J Ophthalmol. 2020 Jul;215:135-140. doi: 10.1016/j.ajo.2020.03.014. Epub 2020 Mar 23.
We sought to investigate the genetic variants associated with the onset and progression of primary open-angle glaucoma (POAG).
Case-control genetic association study.
Japanese POAG patients (n = 505) and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG that can be classified into those associated with intraocular pressure (IOP) elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (non-IOP-related genetic variants). The total number of risk alleles of the 17 IOP-related and 5 non-IOP-related genetic variants were calculated as the genetic risk score (GRS), and the associations between the GRS and family history of glaucoma as an indicator of POAG onset and age at the diagnosis of glaucoma as an indicator of POAG progression were evaluated.
There was a significant association (P = .014; odds ratio 1.26 per GRS) between the non-IOP-related GRS, but not IOP-related GRS, and a family history of glaucoma in POAG. As the non-IOP-related GRS increased, the risk of a family history of glaucoma increased. In contrast, a significant association (P = .0014; β = -0.14) was found between the IOP-related GRS, but not non-IOP-related GRS, and age at the diagnosis of glaucoma. As the IOP-related GRS increased, age at the diagnosis of glaucoma decreased.
The results indicate that non-IOP-related (optic nerve vulnerability) rather than IOP-related (IOP elevation) genetic variants may play an important role in the onset of POAG (family history of glaucoma) and that IOP-related rather than non-IOP-related genetic variants may play an important role in its progression (age at the diagnosis of glaucoma).
我们旨在研究与原发性开角型青光眼（POAG）发病和进展相关的遗传变异。
病例对照遗传关联研究。
对日本 POAG 患者（n=505）和对照受试者（n=246）进行了 22 种易患 POAG 的遗传变异的基因分型，这些变异可分为与眼压（IOP）升高相关的（与 IOP 相关的遗传变异）和与 IOP 无关的视神经脆弱性相关的遗传变异（与 IOP 无关的遗传变异）。将 17 个与 IOP 相关和 5 个与 IOP 无关的遗传变异的风险等位基因总数计算为遗传风险评分（GRS），并评估 GRS 与青光眼家族史（作为 POAG 发病的指标）和青光眼诊断年龄（作为 POAG 进展的指标）之间的关系。
与 IOP 相关的 GRS 与 POAG 家族史之间存在显著关联（P=0.014；每增加 GRS 风险等位基因，比值比为 1.26），而非 IOP 相关的 GRS 则无此关联。随着非 IOP 相关 GRS 的增加，青光眼家族史的风险增加。相比之下，IOP 相关的 GRS 与青光眼诊断年龄之间存在显著关联（P=0.0014；β=-0.14），而非 IOP 相关的 GRS 则无此关联。随着 IOP 相关 GRS 的增加，青光眼诊断年龄降低。
结果表明，非 IOP 相关（视神经脆弱性）而非 IOP 相关（IOP 升高）的遗传变异可能在 POAG（青光眼家族史）的发病中起重要作用，而 IOP 相关而非非 IOP 相关的遗传变异可能在其进展（青光眼诊断年龄）中起重要作用。
