Mabuchi Fumihiko, Tanaka-Mabuchi Nakako, Sakurada Yoichi, Yoneyama Seigo, Yamagata Zentaro, Kashiwagi Kenji
Department of Ophthalmology.
Department of Rheumatology.
J Glaucoma. 2025 Jan 1;34(1):7-12. doi: 10.1097/IJG.0000000000002510. Epub 2024 Oct 22.
The genetic risk score (GRS) of genetic variants associated with intraocular pressure (IOP) elevation, but not those associated with optic nerve vulnerability, was associated with a history of glaucoma surgery in Japanese patients with primary open angle glaucoma (POAG).
To investigate genetic variants associated with a history of glaucoma surgery in Japanese patients with POAG.
Japanese patients with POAG (n = 468), including normal tension glaucoma (n = 246) and high tension glaucoma (n = 222), and control subjects (n = 246) were genotyped for 22 genetic variants predisposing to POAG, which can be classified into those associated with IOP elevation (IOP-related genetic variants) and optic nerve vulnerability independent of IOP (optic nerve-related genetic variants). The unweighted and weighted GRSs of 17 IOP-related, 5 optic nerve-related, and all 22 genetic variants were calculated, and the association between the GRS and a history of glaucoma surgery was evaluated.
There was a significant association (odds ratio 1.13 per unweighted GRS, 95% CI: 1.03 to 1.24, P = 0.0093) between IOP-related unweighted GRS and a history of glaucoma surgery. A significant association (odds ratio 1.09 per 0.1 weighted GRS, 95% CI: 1.04 to 1.14, P = 0.00022) was also found between IOP-related weighted GRS and a history of glaucoma surgery. The IOP-related GRS was positively correlated with the need for glaucoma surgery. The mean of IOP-related unweighted and weighted GRS in patients with POAG with a history of glaucoma surgery were significantly higher ( P = 0.013 and P = 0.00031, respectively) than those in patients with POAG without a history of glaucoma surgery.
IOP-related, but not optic nerve-related, genetic variants were associated with a history of glaucoma surgery in Japanese patients with POAG. These results indicate that IOP elevation induced by IOP-related genetic variants rather than optic nerve vulnerability induced by optic nerve-related genetic variants may play an important role in requiring glaucoma surgery.
在日本原发性开角型青光眼（POAG）患者中，与眼压（IOP）升高相关的基因变异的遗传风险评分（GRS），而非与视神经易损性相关的基因变异的遗传风险评分，与青光眼手术史相关。
研究日本POAG患者中与青光眼手术史相关的基因变异。
对468例日本POAG患者（包括246例正常眼压性青光眼患者和222例高眼压性青光眼患者）以及246例对照受试者进行基因分型，检测22种易导致POAG的基因变异，这些变异可分为与IOP升高相关的变异（IOP相关基因变异）和与IOP无关的视神经易损性相关变异（视神经相关基因变异）。计算17种IOP相关、5种视神经相关及所有22种基因变异的未加权和加权GRS，并评估GRS与青光眼手术史之间的关联。
IOP相关的未加权GRS与青光眼手术史之间存在显著关联（未加权GRS每增加1，比值比为1.13，95%置信区间：1.03至1.24，P = 0.0093）。IOP相关的加权GRS与青光眼手术史之间也存在显著关联（加权GRS每增加0.1，比值比为1.09，95%置信区间：1.04至1.14，P = 0.0oo22）。IOP相关的GRS与青光眼手术需求呈正相关。有青光眼手术史的POAG患者的IOP相关未加权和加权GRS平均值显著高于无青光眼手术史的POAG患者（分别为P = 0.013和P = 0.00031）。
在日本POAG患者中，与IOP相关而非与视神经相关的基因变异与青光眼手术史相关。这些结果表明，由IOP相关基因变异引起的IOP升高而非由视神经相关基因变异引起的视神经易损性，可能在青光眼手术需求中起重要作用。
