Dietzel Martha, Pauleikhoff Daniel, Arning Astrid, Heimes Britta, Lommatzsch Albrecht, Stoll Monika, Hense Hans-Werner
Institute of Epidemiology and Social Medicine, University of Münster, Albert-Schweitzer-Campus 1-D 3, 48129, Münster, Germany,
Graefes Arch Clin Exp Ophthalmol. 2014 Aug;252(8):1273-81. doi: 10.1007/s00417-014-2690-7. Epub 2014 Jun 28.
Genetic factors contribute to the development and progression of age-related macular degeneration (AMD). We aimed to assess the association of drusen as phenotypic characteristics of early AMD and their progression with polymorphisms in the CFH, ABCA1, and ARMS2 genes.
In the Münster Aging and Retina Study (MARS), drusen were detected in 406 patients with early AMD and 170 healthy controls according to the International Classification using fundus photographs, with a follow-up examination after 2.6 years (median). Six drusen features were assessed: drusen number (</≥20); confluence of drusen (</≥50 %), largest drusen size (</≥175 μm); area occupied by drusen (</≥10 %); most frequent drusen size (</≥175 μm), and presence of soft, indistinct drusen (no/yes). Based on these features, an unweighted summary drusen severity score (DSS; categorized in "low", "intermediate" and "high") was calculated. The relationship of each drusen feature and the DSS with CFH rs1061170, ABCA1 rs1883025, and ARMS2 rs10490924 at baseline and after 2.6 years was analyzed using multivariate logistic regression models.
Cross-sectionally, each drusen feature was associated with a higher frequency of the CFH and ARMS2 risk variants. Compared to healthy eyes, the CFH risk variant was more common in eyes with early as well as advanced drusen features, while the ARMS2 variant was only associated with advanced drusen. After 2.6 years, 43 % of the eyes showed a progression of at least 1 unit in the DSS. The progression from low to higher DSS was inversely associated with ABCA1 (OR = 0.54), and the progression from intermediate to high DSS was positively related to CFH rs1061170 (OR = 2.3; p < 0.05 for each).
Variants in CFH, ABCA1, and ARMS2 genes are related to the presence and progression of drusen in early AMD. CFH and, inversely, ABCA1 seem to be involved in early drusen development, while the role of ARMS2 is more pronounced in advanced stages of early AMD.
遗传因素在年龄相关性黄斑变性（AMD）的发生和发展过程中发挥作用。我们旨在评估作为早期AMD表型特征的玻璃膜疣及其进展与CFH、ABCA1和ARMS2基因多态性之间的关联。
在明斯特衰老与视网膜研究（MARS）中，根据国际分类标准，通过眼底照片在406例早期AMD患者和170名健康对照者中检测玻璃膜疣，并在2.6年（中位数）后进行随访检查。评估了六个玻璃膜疣特征：玻璃膜疣数量（＜/≥20个）；玻璃膜疣融合情况（＜/≥50%）；最大玻璃膜疣大小（＜/≥175μm）；玻璃膜疣占据面积（＜/≥10%）；最常见玻璃膜疣大小（＜/≥175μm）；以及软性、边界不清的玻璃膜疣的存在情况（无/有）。基于这些特征，计算了一个未加权的玻璃膜疣严重程度综合评分（DSS；分为“低”、“中”和“高”）。使用多变量逻辑回归模型分析了每个玻璃膜疣特征和DSS与基线时以及2.6年后CFH rs1061170、ABCA1 rs1883025和ARMS2 rs10490924之间的关系。
横断面分析显示，每个玻璃膜疣特征都与CFH和ARMS2风险变异的较高频率相关。与健康眼睛相比，CFH风险变异在具有早期和晚期玻璃膜疣特征的眼睛中更为常见，而ARMS2变异仅与晚期玻璃膜疣相关。2.6年后，43%的眼睛DSS至少进展了1个单位。从低DSS向高DSS的进展与ABCA1呈负相关（OR = 0.54），从中等DSS向高DSS的进展与CFH rs1061170呈正相关（OR = 2.3；两者p均＜0.05）。
CFH、ABCA1和ARMS2基因的变异与早期AMD中玻璃膜疣的存在和进展有关。CFH以及相反的ABCA1似乎参与早期玻璃膜疣的形成，而ARMS2在早期AMD的晚期阶段作用更为明显。
