Centre for Vision and Vascular Science, Queen's University Belfast, Belfast, Ireland.
Retina. 2012 Oct;32(9):1950-8. doi: 10.1097/IAE.0b013e31824dadf1.
To examine associations between recognized genetic susceptibility loci and angiographic subphenotypes of the neovascular variant of age-related macular degeneration (nvAMD).
Participants (247 nvAMD, 52 early age-related macular degeneration [AMD], and 103 controls) were genotyped (complement factor H and ARMS2/HTRA1). nvAMD participants were assigned to one of two subcategories: mainly classic or mainly occult (based on the proportions of classic and occult choroidal neovascularization). nvAMD and early AMD were reassigned to two groups based on the extent and severity of drusen (retinal pigment epithelium dysfunction or not). Univariate and multivariate analysis were used to examine for associations between participant characteristics and genetic loci after adjusting for age, smoking status, and history of cardiovascular disease.
Univariate analysis confirmed the known significant associations between AMD stage and age, hypertension, and a history of cardiovascular disease. Those with retinal pigment epithelium dysfunction (F = 5.46; P = 0.02) or a positive smoking history (F = 3.89; P = 0.05) were more likely to have been classified as having mainly an occult rather than a mainly classic lesion. Multivariate analysis showed that significant associations were noted with the number of ARMS2/HTRA1 risk alleles (P < 0.001), smoking (ever vs. never) (P = 0.03), and cardiovascular disease (P = 0.01). With early AMD as the reference category, the mainly classic group exhibited significant associations with the number of ARMS2/HTRA1 risk alleles present (P < 0.001) and cardiovascular disease (P = 0.02). When mainly classic was compared with mainly occult, the latter was associated with the ARMS2/HTRA1 locus (P = 0.02).
ARMS2/HTRA1 risk genotype may play a role in determining neovascular subphenotype, whereas genetics/demographics, smoking, and systemic health factors contribute to the development of advanced AMD in the presence of early AMD.
研究已识别的遗传易感性基因座与年龄相关性黄斑变性（AMD）新生血管型（nvAMD）的血管生成亚型之间的关联。
对 247 例 nvAMD、52 例早期 AMD 和 103 例对照者进行基因分型（补体因子 H 和 ARMS2/HTRA1）。根据经典型和隐匿型脉络膜新生血管化的比例，将 nvAMD 患者分为主要经典型或主要隐匿型亚组。根据年龄相关性黄斑变性的程度和严重程度（视网膜色素上皮功能障碍与否），将 nvAMD 和早期 AMD 重新分为两组。采用单变量和多变量分析，在调整年龄、吸烟状况和心血管疾病史后，检验参与者特征与遗传位点之间的关联。
单变量分析证实了 AMD 分期与年龄、高血压和心血管疾病史之间的已知显著关联。视网膜色素上皮功能障碍（F = 5.46；P = 0.02）或有吸烟史（F = 3.89；P = 0.05）者更有可能被归类为隐匿型病变为主，而非经典型病变为主。多变量分析显示，ARMS2/HTRA1 风险等位基因数量（P < 0.001）、吸烟状况（曾经吸烟 vs. 从不吸烟）（P = 0.03）和心血管疾病（P = 0.01）与显著关联。与早期 AMD 作为参考类别相比，主要经典型组 ARMS2/HTRA1 风险等位基因数量显著相关（P < 0.001），且与心血管疾病相关（P = 0.02）。与主要隐匿型相比，主要经典型与 ARMS2/HTRA1 基因座相关（P = 0.02）。
ARMS2/HTRA1 风险基因型可能在决定新生血管亚型方面发挥作用，而遗传学/人口统计学、吸烟和系统性健康因素在早期 AMD 存在的情况下促进了晚期 AMD 的发生。
