Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Preventive Medicine and Genetics, Genomics & Informatics, University of Tennessee Health Science Center, Memphis, Tennessee.
Ophthalmology. 2019 Nov;126(11):1541-1548. doi: 10.1016/j.ophtha.2019.06.004. Epub 2019 Jun 12.
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).
Post hoc analysis of a randomized trial.
White AREDS2 participants.
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.
The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD.
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 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.
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).
评估与年龄相关性黄斑变性（AMD）相关的 2 个主要基因座（补体因子 H [CFH]或年龄相关性黄斑变性易感性 2 [ARMS2]）的基因型是否会影响口服营养素治疗年龄相关性眼病研究 2（AREDS2）中 AMD 的疗效。
随机试验的事后分析。
白种人 AREDS2 参与者。
将双侧大玻璃膜疣或 1 只眼晚期 AMD 的 AREDS2 参与者（n=4203）随机分配接受叶黄素和玉米黄质、ω-3 脂肪酸、两者或安慰剂治疗，大多数参与者还接受了 AREDS 补充剂。二次随机评估了 4 种治疗组的改良 AREDS 补充剂：降低锌剂量、不使用β-胡萝卜素、两者或不进行修改。为了评估向晚期 AMD 的进展，在基线和每年的研究访视时获取眼底照片，并在研究访视和 6 个月的临时电话访视时获取晚期 AMD 的治疗史。对 rs1061170 单核苷酸多态性进行基因分型在 CFH 和 rs10490924 在 ARMS2。使用双眼进行双变量脆弱性模型分析，包括基因-补充剂相互作用项，并调整年龄、性别、教育水平和吸烟状况。评估了基因型与 AREDS2 补充剂反应之间的主要治疗效果，以及叶黄素加玉米黄质与β-胡萝卜素的直接比较。
基因型与 AREDS2 补充剂对晚期 AMD、任何地理萎缩（GA）和新生血管性 AMD 进展的反应之间的相互作用。
2775 只无基线晚期 AMD 的眼睛（1684 名参与者）获得完整数据。参与者（平均年龄±标准差，72.1±7.7 岁；58.5%女性）中位随访 5 年。ARMS2 风险等位基因与晚期 AMD 和新生血管性 AMD 的进展显著相关（P=2.40×10 和 P=0.002），但与任何 GA 无关（P=0.097）。CFH 风险等位基因与 AMD 进展无关。基因型不能显著改变对任何 AREDS2 补充剂的反应。
CFH 和 ARMS2 风险等位基因不能改变 AREDS2 营养补充剂对晚期 AMD（GA 和新生血管性 AMD）进展的反应。
