Genetic Variants Associated With a History of Glaucoma Surgery in Japanese Patients With Primary Open Angle Glaucoma.

Abstract

Prcis: 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).

Objective: To investigate genetic variants associated with a history of glaucoma surgery in Japanese patients with POAG.

Methods: 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.

Results: 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.

Conclusions: 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.