Department of Ophthalmology, Saitama Medical University, Iruma, Saitama, Japan.
Ophthalmology. 2010 May;117(5):928-38. doi: 10.1016/j.ophtha.2009.10.001. Epub 2010 Feb 4.
To describe phenotype and genotype characteristics of age-related macular degeneration (AMD) in Japanese patients.
A case-control study.
A total of 550 case-control samples composed of 408 consecutive AMD cases and 142 controls.
Clinical information assessing age, gender, affected eyes, fundus features, and fluorescein/indocyanine green angiograms were systematically evaluated. Four single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the complement factor H (CFH) gene, 1 SNP (rs11200638) in the high-temperature requirement factor A1 (HTRA1) gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were assessed using TaqMan technology.
The clinical phenotype information and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms.
Of Japanese patients with neovascular AMD (nAMD), 219 (58.7%) had typical nAMD and 154 (41.3%) had polypoidal choroidal vasculopathy (PCV). The frequency of bilateral exudative involvement was similar between typical nAMD (15.5%) and PCV (13.6%) (P = 0.613). Significant soft drusen were observed in the fellow eyes of 88 (47.6%) of 185 patients with unilateral typical nAMD and in 25 (18.8%) of 133 patients with unilateral PCV (P = 1.24x10(-7)). A serous pigment epithelium detachment was seen in 55 (25.1%) of 219 patients with typical nAMD and in 64 (41.6%) of 154 patients with PCV. A significant association was noted in CFH-rs800292, CFH-rs1410996, CFH-rs2274700, and HTRA1-rs11200638 with AMD development (P = 2.36x10(-5), 7.18x10(-5), 7.18x10(-5), 2.70x10(-7), respectively; population attributable risk = 57.3%, 57.8%, 57.8%, and 58.9%, respectively). We estimated the highest-risk group to have an approximately 70-fold greater risk of nAMD compared with the lowest-risk group when analyzing a combination of 4 SNPs in the CFH and HTRA1 genes.
The Japanese AMD phenotype is characterized by a higher frequency of PCV, male predominance, and lower frequency of bilateral presentation compared with Caucasian AMD. Genotype analyses demonstrate a significant population attributable risk for SNPs in the CFH and HTRA1 genes and demonstrate joint effects for both genes. Gene variants in both CFH and HTRA1 contribute significantly to the AMD phenotype in a Japanese population.
描述与年龄相关的黄斑变性（AMD）相关的日本患者的表型和基因型特征。
病例对照研究。
总共包括 408 例连续 AMD 病例和 142 例对照的 550 例病例对照样本。
系统评估了评估年龄、性别、受影响的眼睛、眼底特征和荧光素/吲哚青绿血管造影的临床信息。补体因子 H（CFH）基因中的 4 个单核苷酸多态性（SNP；rs800292、rs1061170、rs1410996、rs2274700）、高温需求因子 A1（HTRA1）基因中的 1 个 SNP（rs11200638）、血管内皮生长因子（VEGF）基因中的 3 个 SNP（rs699947、rs1570360、rs2010963）和色素上皮衍生因子（PEDF）基因中的 4 个 SNP（rs12150053、rs12948385、rs9913583、rs1136287）采用 TaqMan 技术进行评估。
CFH、HTRA1、VEGF 和 PEDF 多态性的临床表型信息和基因型。
在日本新生血管性 AMD（nAMD）患者中，219 例（58.7%）为典型 nAMD，154 例（41.3%）为息肉样脉络膜血管病变（PCV）。典型 nAMD（15.5%）和 PCV（13.6%）之间双侧渗出性受累的频率相似（P = 0.613）。在 185 例单侧典型 nAMD 患者的对侧眼中观察到明显的软性渗出物，在 133 例单侧 PCV 患者的 25 例（18.8%）中观察到明显的软性渗出物（P = 1.24x10(-7)）。在 219 例典型 nAMD 患者中观察到浆液性色素上皮脱离，在 154 例 PCV 患者中观察到 64 例（41.6%）（P = 2.36x10(-5)）。在 AMD 发展中，CFH-rs800292、CFH-rs1410996、CFH-rs2274700 和 HTRA1-rs11200638 存在显著关联（P = 2.36x10(-5)、7.18x10(-5)、7.18x10(-5)、2.70x10(-7)，分别；人群归因风险 = 57.3%、57.8%、57.8%和 58.9%，分别）。当分析 CFH 和 HTRA1 基因中的 4 个 SNP 的组合时，我们估计最高风险组与最低风险组相比，nAMD 的风险约增加 70 倍。
与高加索 AMD 相比，日本 AMD 的表型特征为 PCV 频率较高、男性优势和双侧表现频率较低。基因型分析表明 CFH 和 HTRA1 基因中的 SNP 具有显著的人群归因风险，并显示出这两个基因的共同作用。CFH 和 HTRA1 中的基因变异显著导致日本人群的 AMD 表型。
