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Genetic Polymorphisms in the Angiotensin II Receptor Gene and Their Association with Open-Angle Glaucoma in a Japanese Population

¹From the Departments of Ophthalmology and ⁸Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan; the ²Department of Ophthalmology, Tokyo Metropolitan Police Hospital, Tokyo, Japan; the ³Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan; the ⁴Department of Ophthalmology, Hamamatsu University School of Medicine, Hamamatsu, Japan; the ⁵Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; the ⁶Department of Ophthalmology and Visual Science, Graduate School of Medical Sciences, Hiroshima University, Hiroshima, Japan; and the ⁷Division of Ophthalmology and Visual Science, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

PURPOSE. The local renin–angiotensin system (RAS) is present in the ciliary body and plays a role in regulating aqueous humor dynamics and thus intraocular pressure (IOP). The purpose of this study was to determine whether gene polymorphisms in the RAS increase the risk of development of glaucoma in the Japanese.

METHODS. A case–control study was performed in 698 Japanese subjects: 190 patients with primary open-angle glaucoma (POAG), 268 patients with normal-tension glaucoma (NTG), and 240 normal subjects. Ten polymorphisms in seven genes—AGT/Thr174Met and AGT/Met235Thr; REN/I8-83GA; ACE/insertion(I)-deletion(D); CMA/–1930AG; AGTR1/–731TG, AGTR1/–521CT, and AGTR1/1166AC; AGTR2/3123CA; and CYP11B2/–344TC were examined. The age, IOP, and visual field defects, all at diagnosis, were examined to determine whether they were associated with the polymorphisms. The effects of oral angiotensin II receptor blocker (ARB) on IOP were examined in association with the AGTR1 and AGTR2 polymorphisms in 20 normal subjects.

RESULTS. Of the 10 polymorphisms, the AGTR2/3123CA polymorphisms had a significantly different distribution in female patients with NTG; the frequency of the CA+AA genotypes was significantly higher than in female control subjects (P = 0.0095 for CC versus CA+AA). Although no significant difference was seen in the clinical characteristics of female patients with NTG who carried the AGTR2/3123CA genotype, patients with CC in the AGTR2 gene had significantly worse visual field scores if they carried ACE/ID+DD (i.e., D carriers; P = 0.012). ARB significantly lowered IOP in normal subjects, but the male subjects with the AGTR2/3123A genotype had significantly less lowering of IOP than those with the C genotype (P = 0.014).

CONCLUSIONS. Angiotensin II receptor gene polymorphisms may be associated with the risk of glaucoma in the Japanese population.

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