Tennessee Retina, PC, Nashville, Tennessee.
Ophthalmology. 2013 Nov;120(11):2317-23. doi: 10.1016/j.ophtha.2013.07.039. Epub 2013 Aug 21.
The Age-Related Eye Disease Study (AREDS) demonstrated that antioxidant and zinc supplementation decreases progression to advanced age-related macular degeneration (AMD) in patients with moderate to severe disease. We evaluated the interaction of genetics and type of nutritional supplement on progression from moderate to advanced AMD.
Genetic analysis of a randomized, prospective clinical trial.
White patients with AREDS category 3 AMD in 1 eye and AREDS categories 1 through 4 AMD in the fellow eye enrolled in the AREDS with available peripheral blood-derived DNA (995).
Subjects were evaluated for known AMD genetic risk markers and treatment category. The progression rate to advanced AMD was analyzed by genotypes and AREDS treatment group using Cox regression.
The effect of inherited gene polymorphisms on treatment group-specific rate of progression to advanced AMD.
Over an average of 10.1 years, individuals with 1 or 2 complement factor H (CFH) risk alleles derived maximum benefit from antioxidants alone. In these patients, the addition of zinc negated the benefits of antioxidants. Treatment with zinc and antioxidants was associated with a risk ratio (RR) of 1.83 with 2 CFH risk alleles (P = 1.03E-02), compared with outcomes for patients without CFH risk alleles. Patients with age-related maculopathy sensitivity 2 (ARMS2) risk alleles derived maximum benefit from zinc-containing regimens, with a deleterious response to antioxidants in the presence of ARMS2 risk alleles. Treatment with antioxidants was associated with an RR of 2.58 for those with 1 ARMS2 risk allele and 3.96 for those with 2 ARMS2 risk alleles (P = 1.04E-6), compared with patients with no ARMS2 risk alleles. Individuals homozygous for CFH and ARMS2 risk alleles derived no benefit from any category of AREDS treatment.
Individuals with moderate AMD could benefit from pharmacogenomic selection of nutritional supplements. In this analysis, patients with no CFH risk alleles and with 1 or 2 ARMS2 risk alleles derived maximum benefit from zinc-only supplementation. Patients with one or two CFH risk alleles and no ARMS2 risk alleles derived maximum benefit from antioxidant-only supplementation; treatment with zinc was associated with increased progression to advanced AMD. These recommendations could lead to improved outcomes through genotype-directed therapy.
年龄相关性眼病研究（AREDS）表明，抗氧化剂和锌补充剂可减少中重度年龄相关性黄斑变性（AMD）患者向晚期 AMD 进展。我们评估了遗传和营养补充类型对从中度到晚期 AMD 进展的相互作用。
一项随机、前瞻性临床试验的遗传分析。
一只眼患有 AREDS 3 类 AMD，另一只眼患有 AREDS 1 至 4 类 AMD 的白种患者，在 AREDS 中入组，并有可用的外周血衍生 DNA（995 例）。
评估受试者的已知 AMD 遗传风险标志物和治疗类别。使用 Cox 回归分析基因型和 AREDS 治疗组对进展为晚期 AMD 的进展率。
遗传基因多态性对特定治疗组进展为晚期 AMD 的影响。
在平均 10.1 年的时间里，1 或 2 个补体因子 H（CFH）风险等位基因的个体从单独使用抗氧化剂中获得最大益处。在这些患者中，锌的添加否定了抗氧化剂的益处。与无 CFH 风险等位基因的患者相比，用锌和抗氧化剂治疗的风险比（RR）为 1.83，具有 2 个 CFH 风险等位基因（P = 1.03E-02）。携带年龄相关性黄斑病变敏感性 2（ARMS2）风险等位基因的患者从含锌方案中获得最大益处，而在存在 ARMS2 风险等位基因的情况下，抗氧化剂的反应是有害的。与无 ARMS2 风险等位基因的患者相比，用抗氧化剂治疗的 RR 为 1 个 ARMS2 风险等位基因的 2.58 和 2 个 ARMS2 风险等位基因的 3.96（P = 1.04E-6）。纯合 CFH 和 ARMS2 风险等位基因的个体不能从任何 AREDS 治疗类别中获益。
患有中度 AMD 的个体可能会受益于营养补充剂的药物基因组选择。在本分析中，无 CFH 风险等位基因且有 1 或 2 个 ARMS2 风险等位基因的患者从仅补锌中获益最大。有一个或两个 CFH 风险等位基因且无 ARMS2 风险等位基因的患者从仅抗氧化剂治疗中获益最大；锌治疗与晚期 AMD 进展增加相关。这些建议可以通过基因指导治疗带来更好的治疗效果。
