PURPOSE To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). DESIGN Post hoc analysis of a randomized trial. PARTICIPANTS White AREDS2 participants. METHODS AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of β-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and β-carotene, were assessed for genotype interaction. MAIN OUTCOME MEASURES The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. RESULTS Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10-5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. CONCLUSIONS CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

中文翻译：

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在年龄相关的眼病研究中，CFH或ARMS2与Omega-3脂肪酸，低锌与高锌，或β-胡萝卜素与叶黄素和玉米黄质的相互作用均不影响年龄相关的黄斑变性的进展：研究2：年龄相关的眼病研究2第18号报告。

目的评估2个主要基因座的基因型是否与年龄相关性黄斑变性（AMD），补体因子H（CFH）或年龄相关性黄斑病变易感性2（ARMS2）相关，请修改对口服营养素的反应以治疗AMD年龄相关性眼疾研究2（AREDS2）。设计随机试验的事后分析。参与者白色AREDS2参与者。方法AREDS2参与者（n = 4203）患双侧大玻璃疣或晚期AMD的一只眼睛被随机分配至叶黄素和玉米黄质，omega-3脂肪酸或安慰剂，并且大多数还接受了AREDS补充剂。二次随机评估的修饰AREDS补品在4个治疗组中：较低的锌剂量，遗漏β-胡萝卜素，两者或无修饰。为了评估晚期AMD的进展，在基线和年度研究访问时获得眼底照片，在研究访问和6个月的临时电话访问中获得晚期AMD的治疗史。对参与者进行CFH基因单核苷酸多态性rs1061170和ARMS2基因rs10490924的基因分型。使用双眼进行了双变量脆弱模型，包括基因-补充相互作用项，并根据年龄，性别，受教育程度和吸烟状况进行了调整。评价了基因型相互作用的主要治疗效果，以及叶黄素加玉米黄质和β-胡萝卜素之间的直接比较。主要观察指标关于晚期AMD，任何地理性萎缩（GA）和新血管性AMD的进展，基因型与对AREDS2补充剂的反应之间的相互作用。结果可获得2775眼无基线晚期AMD的完整数据（1684名参与者）。参与者（平均年龄±标准差，72.1±7.7岁；女性58.5％）得到了5年的中位随访。ARMS2风险等位基因与晚期AMD和新血管性AMD的进展显着相关（分别为P = 2.40×10-5和P = 0.002），而与GA无关（P = 0.097）。CFH风险等位基因与AMD进展无关。基因型没有显着改变对任何AREDS2补充剂的反应。结论CFH和ARMS2风险等位基因不会改变对晚期AMD（GA和新血管性AMD）进展对AREDS2营养补充剂的反应。ARMS2风险等位基因与晚期AMD和新血管性AMD的进展显着相关（分别为P = 2.40×10-5和P = 0.002），而与GA无关（P = 0.097）。CFH风险等位基因与AMD进展无关。基因型没有显着改变对任何AREDS2补充剂的反应。结论CFH和ARMS2风险等位基因不会改变对晚期AMD（GA和新血管性AMD）进展对AREDS2营养补充剂的反应。ARMS2风险等位基因与晚期AMD和新血管性AMD的进展显着相关（分别为P = 2.40×10-5和P = 0.002），而与GA无关（P = 0.097）。CFH风险等位基因与AMD进展无关。基因型没有显着改变对任何AREDS2补充剂的反应。结论CFH和ARMS2风险等位基因不会改变对晚期AMD（GA和新血管性AMD）进展对AREDS2营养补充剂的反应。