Genetic polymorphisms in the angiotensin II receptor gene and their association with open-angle glaucoma in a Japanese population
Genetic polymorphisms in the angiotensin II receptor gene and their association with open-angle glaucoma in a Japanese population
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DOI：
10.1167/iovs.04-1100
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Miyaki, K
中科院分区：
文献类型：
--
作者：
Hashizume, K;Mashima, Y;Miyaki, K
目的.局部的肾素-血管紧张素系统（RAS）存在于睫状体中，并且在调节房水动力学和因此眼内压（IOP）中起作用。本研究的目的是确定RAS基因多态性是否会增加日本人青光眼发生的风险。在698名日本受试者中进行了病例对照研究：190名原发性开角型青光眼（POAG）患者，268名正常眼压性青光眼（NTG）患者和240名正常受试者。检测了AGT/Thr 174 Met和AGT/Met 235 Thr; REN/I8- 83 G-> A; ACE/插入（I）-缺失（D）; CMA/-1930 A-> G; AGTR 1/-731 T-> G; AGTR 1/-521 C-> T和AGTR 1/1166 A-> C; AGTR 2/3123 C-> A;和CYP 11 B2/-344 T-> C 7个基因的10个多态性。年龄，眼压，视野缺损，所有在诊断，进行了检查，以确定他们是否与多态性。在20名正常受试者中检测了口服血管紧张素II受体阻滞剂（ARB）对IOP的影响与AGTR 1和AGTR 2多态性的关系。在10种多态性中，AGTR 2/3123 C-> A多态性在女性NTG患者中的分布有显著差异; CA + AA基因型的频率显著高于女性对照受试者（CC与CA + AA的P = 0.0095）。虽然携带AGTR 2/3123 C-> A基因型的NTG女性患者的临床特征没有显著差异，但如果携带ACE/ID + DD（即，D携带者; P + 0.012）。ARB可显著降低正常人的眼压，但AGTR 2/3123 A基因型男性受试者的眼压降低程度显著低于C基因型（P = 0.014）。血管紧张素II受体基因多态性可能与日本人群青光眼的风险相关。
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/I8-83G -> A; ACE/insertion(I)-deletion(D); CMA/-1930A -> G; AGTR1/-731T -> G, AGTR1/-521C -> T, and AGTR1/1166A -> C; AGTR2/3123C -> A; and CYP11B2/-344T -> C 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 AGTR2/3123C -> A 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 AGTR2/3123C -> A 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.