Tsuchihashi Takashi, Mori Keisuke, Horie-Inoue Kuniko, Okazaki Yasushi, Awata Takuya, Inoue Satoshi, Yoneya Shin
Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clin Ophthalmol. 2014 Dec 5;8:2471-8. doi: 10.2147/OPTH.S71305. eCollection 2014.
This study aimed to demonstrate the phenotypic and genotypic factors associated with photodynamic therapy (PDT) for age-related macular degeneration (AMD).
The study included 149 patients with exudative AMD treated by PDT. Eight phenotypic factors and ten genotypic factors for three single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996) in the complement factor H (CFH) gene, rs 11200638-SNP in the high temperature requirement A-1 (HTRA1) gene, two SNPs (rs699947, rs2010963) in the vascular endothelial growth factor (VEGF) gene, and four SNPs (rs12948385, rs12150053, rs9913583, rs1136287) in the pigment epithelium-derived factor (PEDF) gene were evaluated.
A significant association with best-corrected visual acuity change was demonstrated in the greatest linear dimension, presence or absence of pigment epithelial detachment, and HTRA1-rs11200638 genotype statistically (P=3.67×10(-4), 1.95×10(-2), 1.24×10(-3), respectively). Best-corrected visual acuity in patients with AA genotype of HTRA1-rs11200638 significantly decreased compared with that in patients with GG genotype (P=1.33×10(-3)). Logistic regression analyses demonstrated HTRA1-rs11200638 genotype was most strongly associated with best-corrected visual acuity outcome from baseline at 12 months after photodynamic therapy (P=4.60×10(-3); odds ratio 2.363; 95% confidence interval 1.303-4.285).
The HTRA1-rs11200638 variant showed the most significant association. Therefore, this variant may be used as a prognostic factor to estimate the PDT response with significant predictive power.
本研究旨在阐明与年龄相关性黄斑变性（AMD）光动力疗法（PDT）相关的表型和基因型因素。
该研究纳入了149例接受PDT治疗的渗出性AMD患者。评估了补体因子H（CFH）基因中三个单核苷酸多态性（SNP；rs800292、rs1061170、rs1410996）的八个表型因素和十个基因型因素、高温需求A-1（HTRA1）基因中的rs11200638-SNP、血管内皮生长因子（VEGF）基因中的两个SNP（rs699947、rs2010963）以及色素上皮衍生因子（PEDF）基因中的四个SNP（rs12948385、rs12150053、rs9913583、rs1136287）。
最大线性尺寸、色素上皮脱离的有无以及HTRA1-rs11200638基因型与最佳矫正视力变化存在显著相关性（P分别为3.67×10⁻⁴、1.95×10⁻²、1.24×10⁻³）。与HTRA1-rs11200638的GG基因型患者相比，AA基因型患者的最佳矫正视力显著下降（P = 1.33×10⁻³）。逻辑回归分析表明，HTRA1-rs11200638基因型与光动力治疗后12个月时基线最佳矫正视力结果的相关性最强（P = 4.60×10⁻³；优势比2.363；95%置信区间1.303 - 4.285）。
HTRA1-rs11200638变异显示出最显著的相关性。因此，该变异可作为一种预后因素，用于评估具有显著预测能力的PDT反应。
