补体因子H Y402H和C反应蛋白多态性与年龄相关性黄斑变性的光动力疗法反应

Complement factor H Y402H and C-reactive protein polymorphism and photodynamic therapy response in age-related macular degeneration.

作者信息

Feng Xuefeng, Xiao Jing, Longville Brooke, Tan Alexander X J, Wu Xia Ni, Cooper Matthew N, McAllister Ian L, Isaacs Timothy, Palmer Lyle J, Constable Ian J

机构信息

Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Australia.

出版信息

Ophthalmology. 2009 Oct;116(10):1908-12.e1. doi: 10.1016/j.ophtha.2009.03.011. Epub 2009 Aug 18.

DOI:10.1016/j.ophtha.2009.03.011

PMID:19692124

Abstract

PURPOSE

To investigate the association between complement factor H (CFH) and C-reactive protein (CRP) genotypes and response to photodynamic therapy (PDT) treatment for neovascular age-related macular degeneration (AMD).

DESIGN

Retrospective cohort study.

PARTICIPANTS

The study cohort consisted of 273 neovascular AMD patients treated with PDT.

METHODS

Genotypes were determined for the common T-->C single nucleotide polymorphism (SNP) in exon 9 of the CFH gene (rs1061170; Y402H), as well as 9 selected tagging SNPs across the CRP gene (rs2808635, rs1417938, rs1800947, rs1130864, rs1205, rs3093077, rs876538, rs876537, and rs1572970). Visual acuity outcome after PDT was retrospectively calculated and patients were classified as PDT-positive responders or PDT-negative responders. Logistic regression analysis was used to evaluate the association between individual SNPs and PDT treatment response while adjusting for relevant covariates.

MAIN OUTCOME MEASURES

Response to PDT treatment defined by visual acuity; genotypes of CFH Y402H and CRP polymorphism.

RESULTS

Of the 273 patients, 75 had a positive response after PDT treatment. The frequency of CC genotype of the CFH Y402H polymorphism in the PDT-positive response group was lower than in the negative PDT response group (26.4% vs 31.6%) but this difference failed to reach statistical significance. Two CRP SNPs (rs2808635 and rs876538) were significantly associated with PDT treatment response. Positive treatment response was seen in individuals homozygous for the minor allele of the rs2808635 (GG; odds ratio [OR], 3.92; 95% confidence interval [CI], 1.40-10.97; P = 0.048) and rs876538 (AA; OR, 6.49; 95% CI, 1.65-25.47; P = 0.048) variants after adjusting for relevant covariates. The remaining 7 CRP genetic variants did not reveal any significant association with treatment response.

CONCLUSIONS

Our data did not show significant association between the CFH Y402H polymorphism and PDT treatment response for neovascular AMD; however, CRP genetic variants were associated with a positive response to PDT treatment for neovascular AMD.

摘要

目的

探讨补体因子H（CFH）和C反应蛋白（CRP）基因多态性与新生血管性年龄相关性黄斑变性（AMD）光动力疗法（PDT）治疗反应之间的关联。

设计

回顾性队列研究。

参与者

研究队列由273例接受PDT治疗的新生血管性AMD患者组成。

方法

测定CFH基因第9外显子常见的T→C单核苷酸多态性（SNP）（rs1061170；Y402H）以及CRP基因上9个选定的标签SNP（rs2808635、rs1417938、rs1800947、rs1130864、rs1205、rs3093077、rs876538、rs876537和rs1572970）的基因型。回顾性计算PDT后的视力结果，并将患者分为PDT阳性反应者或PDT阴性反应者。采用逻辑回归分析评估个体SNP与PDT治疗反应之间的关联，同时对相关协变量进行校正。

主要观察指标

以视力定义的PDT治疗反应；CFH Y402H基因型和CRP基因多态性。

结果

273例患者中，75例在PDT治疗后有阳性反应。PDT阳性反应组中CFH Y402H多态性的CC基因型频率低于PDT阴性反应组（26.4%对31.6%），但这种差异未达到统计学意义。两个CRP SNP（rs2808635和rs876538）与PDT治疗反应显著相关。在校正相关协变量后，rs2808635（GG；优势比[OR]，3.92；95%置信区间[CI]，1.40 - 1,0.97；P = 0.048）和rs876538（AA；OR，6.49；95% CI，1.65 - 25.47；P = 0.048）变异的纯合子个体出现阳性治疗反应。其余7个CRP基因变异与治疗反应未显示出任何显著关联。