Fumihiko Mabuchi1, Nakako Mabuchi2, Yoichi Sakurada2, Seigo Yoneyama2, Kenji Kashiwagi2, Hiroyuki Iijima2, Zentaro Yamagata3, Mitsuko Takamoto4, Makoto Aihara5, Takeshi Iwata6, Kazuki Hashimoto7, Kota Sato8, Yukihiro Shiga9, Koji M Nishiguchi10, Toru Nakazawa11, Masato Akiyama12, Kazuhide Kawase13, Mineo Ozaki14, Makoto Araie15. 1. Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. Electronic address: mabuchif-oph@umin.ac.jp. 2. Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. 3. Department of Health Sciences, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. 4. Department of Ophthalmology, Saitama Red Cross Hospital, Saitama, Japan. 5. Department of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. 6. Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan. 7. Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan. 8. Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan; Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Miyagi, Japan. 9. Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan. 10. Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan. 11. Department of Ophthalmology, Tohoku University Graduate School of Medicine, Miyagi, Japan; Collaborative Program for Ophthalmic Drug Discovery, Tohoku University Graduate School of Medicine, Miyagi, Japan; Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Miyagi, Japan; Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan. 12. Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 13. Department of Ophthalmolgy, Gifu University Graduate School of Medicine, Gifu, Japan. 14. Ozaki Eye Hospital, Miyazaki, Japan. 15. Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Tokyo, Japan.
Abstract
PURPOSE: We sought to investigate the genetic variants associated with the onset and progression of primary open-angle glaucoma (POAG). DESIGN: Case-control genetic association study. METHODS: 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. RESULTS: 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. CONCLUSION: 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).
PURPOSE: We sought to investigate the genetic variants associated with the onset and progression of primary open-angle glaucoma (POAG). DESIGN: Case-control genetic association study. METHODS: 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. RESULTS: 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. CONCLUSION: 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).