Section of Clinical Epidemiology, Institute of Epidemiology and Social Medicine, University of Muenster, Muenster, Germany.
Eye (Lond). 2009 Dec;23(12):2238-44. doi: 10.1038/eye.2008.426.
Little is known about the role of genetic variants in the early stages of age-related macular degeneration (AMD). We aimed to investigate how genetic variations within five well-defined genes relate to AMD severity.
We analysed SNPs in the genes for complement factor H (CFH), age-related maculopathy susceptibility (ARMS2), HtrA serine peptidase 1 (HtrA1), complement factor B (CFB), and complement component 2 (C2)in 183 controls and 730 patients with increasing severity of AMD from the Muenster aging and retina study (MARS). Severity scoring was based on the Rotterdam classification of fundus photographs.
Compared with controls, patients with very early AMD showed a significantly increased minor allele frequency (MAF) only for CFH-rs1061170. With increasing severity of AMD, SNPs in CFH-rs1061170,as well as ARMS2-rs10490924, became consistently more common (P<0.001). Likewise, HtrA1-rs11200638 was less clearly associated with AMD severity, whereas C2-rs9332739 and CFB-rs641153 showed no relation. Multifactorial models confirmed CFH and ARMS2 as major determinants of AMD severity, whereas addition of HtrA1, C2 and CFB did not improve model prediction. In the models, age did not contribute to very early but to all more severe AMD stages, whereas smoking history had a significant impact only for late AMD.
Our findings indicate that the CFH gene is involved in the onset of AMD, whereas both, the CFH and ARMS2 genes, and more weakly, the HtrA1 gene, appear to account for the advancement of AMD. The results for SNPs in the C2 and CFB genes were inconclusive. Genetic factors dominated in their impact over age and smoking history.
关于遗传变异在年龄相关性黄斑变性（AMD）早期阶段的作用知之甚少。我们旨在研究五个明确界定的基因内的遗传变异与 AMD 严重程度的关系。
我们分析了 Muenster 衰老与视网膜研究（MARS）中 183 名对照者和 730 名 AMD 严重程度逐渐增加的患者中补体因子 H（CFH）、年龄相关性黄斑病变易感性（ARMS2）、HtrA 丝氨酸肽酶 1（HtrA1）、补体因子 B（CFB）和补体成分 2（C2）基因中的 SNP。严重程度评分基于眼底照片的 Rotterdam 分类。
与对照组相比，早期 AMD 患者仅在 CFH-rs1061170 中显示出显著增加的次要等位基因频率（MAF）。随着 AMD 严重程度的增加，CFH-rs1061170 以及 ARMS2-rs10490924 的 SNP 变得越来越常见（P<0.001）。同样，HtrA1-rs11200638 与 AMD 严重程度的相关性不太明显，而 C2-rs9332739 和 CFB-rs641153 则没有关系。多因素模型证实 CFH 和 ARMS2 是 AMD 严重程度的主要决定因素，而添加 HtrA1、C2 和 CFB 并不能改善模型预测。在模型中，年龄对早期 AMD 没有贡献，但对所有更严重的 AMD 阶段都有贡献，而吸烟史仅对晚期 AMD 有显著影响。
我们的研究结果表明，CFH 基因参与了 AMD 的发病，而 CFH 和 ARMS2 基因以及较弱的 HtrA1 基因似乎都与 AMD 的进展有关。C2 和 CFB 基因中的 SNP 结果不确定。遗传因素在其对年龄和吸烟史的影响方面占主导地位。
