Complement Factor H and High-Temperature Requirement A-1 Genotypes and Treatment Response of Age-related Macular Degeneration
Complement Factor H and High-Temperature Requirement A-1 Genotypes and Treatment Response of Age-related Macular Degeneration
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DOI：
10.1016/j.ophtha.2010.04.007
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发表时间：
2011-01-01
期刊：
影响因子：
13.7
通讯作者：
Yoneya, Shin
中科院分区：
文献类型：
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作者：
Tsuchihashi, Takashi;Mori, Keisuke;Yoneya, Shin
目的：确定日本人群中补体因子H（CFH）、高温需要A-1（HTRA 1）、血管内皮生长因子（VEGF）和色素上皮衍生因子（PEDF）基因型与光动力疗法（PDT）治疗年龄相关性黄斑变性（AMD）的反应之间是否存在关联。设计：前瞻性病例对照研究。参与者：在日本琦玉县琦玉医科大学医院眼科前瞻性招募了110例接受维替泊芬PDT治疗的渗出性AMD患者。（SNP; rs 800292、rs 1061170、rs 1410996、rs 2274700），HTRA 1基因中的一个rs 11200638-SNP，3个SNP VEGF基因中的（rs699947、rs 1570360、rs 2010963）和4个SNP使用TaqMan测定法检测PEDF基因中的rs 12150053、rs 12948385、rs 9913583、rs 1136287）。治疗结果和CFH、HTRA 1、VEGF和PEDF多态性的基因型。PDT治疗后1年，HTRA 1-rs 11200638 GG基因型患者的最佳矫正视力显著高于GA或AA基因型患者（P = 2.9 × 10（-2），7.0 × 10（-4））。PDT后12个月内的复发率也与HTRA 1-rs 11200638基因型相关（P = 3.12 x 10（-2））。HTRA 1-rs 11200638 AA基因型患者的复发风险比GG基因型患者高约6倍（P = 5.58 x 10 - 3）。CFH-rs 1410996/-rs 2274700基因型从初始治疗到复发的平均时间间隔存在显著性差异（P = 8.50 × 10（-3））。结论：HTRA 1-rs 11200638和CFH-rs 1410996/-rs 2274700变异体与本研究人群中PDT的应答相关。这些变体可用于遗传生物标志物，以估计视觉结果和PDT响应中的复发，具有显著的预测能力。
Purpose: To determine whether there is an association between complement factor H (CFH), high-temperature requirement A-1 (HTRA1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) genotypes and response to treatment with photodynamic therapy (PDT) for age-related macular degeneration (AMD) in a Japanese population.Design: Prospective, case-control study.Participants: One hundred ten patients with exudative AMD treated by verteporfin PDT were recruited prospectively at the Department of Ophthalmology, Saitama Medical University Hospital, Saitama, Japan.Methods: The patients were genotyped for 4 single nucleotide polymorphisms (SNPs; rs800292, rs1061170, rs1410996, rs2274700) in the CFH gene, a rs11200638-SNP in the HTRA1 gene, 3 SNPs (rs699947, rs1570360, rs2010963) in the VEGF gene, and 4 SNPs (rs12150053, rs12948385, rs9913583, rs1136287) in the PEDF gene using a TaqMan assay.Main Outcome Measures: The treatment outcomes and genotypes of CFH, HTRA1, VEGF, and PEDF polymorphisms.Results: Best-corrected visual acuity 1 year after PDT was significantly increased in patients with the HTRA1-rs11200638 GG genotype as compared with patients with the GA or AA genotypes (P = 2.9 x 10(-2), 7.0 x 10(-4), respectively). The rate of recurrence in the 12-month period after PDT was also associated with HTRA1-rs11200638 genotype (P = 3.12 x 10(-2)). Patients with the AA genotype of HTRA1-rs11200638 had an approximately 6-fold greater risk of the recurrence than patients with the GG genotype (P = 5.58 x 10(-3)). Significant differences were demonstrated in the mean time interval from the initial treatment to the time of recurrence for the genotypes of CFH-rs1410996/-rs2274700 (P = 8.50 x 10(-3)).Conclusions: The HTRA1-rs11200638 and CFH-rs1410996/-rs2274700 variants were associated with response to PDT in this study population. These variants may be used for genetic biomarkers to estimate visual outcomes and recurrences in the response to PDT with significant predictive power.