CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration
CFH and LOC387715/ARMS2 genotypes and treatment with antioxidants and zinc for age-related macular degeneration
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CFH 和 LOC387715/ARMS2 基因型以及抗氧化剂和锌治疗年龄相关性黄斑变性
DOI：
10.1016/j.ophtha.2008.01.036
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发表时间：
2008-06-01
期刊：
影响因子：
13.7
通讯作者：
Seddon, Johanna M.
中科院分区：
文献类型：
--
作者：
Klein, Michael L.;Francis, Peter J.;Seddon, Johanna M.
目的：为了确定CFH和LOC 387715/ARMS 2基因型是否会影响对AREDS型营养补充剂（抗氧化剂和锌）的治疗反应，设计：对随机对照临床试验中的参与者进行回顾性分析，该研究是一项与眼部疾病相关的研究（AREDS）。参与者和/或对照：876名AREDS研究参与者被认为是发生晚期年龄相关性黄斑变性（AMD）的高风险。研究方法：使用从876名白色参与者的静脉血中提取的DNA，这些参与者被认为是进展为晚期AMD的高风险人群，作者对CFH（Y 402 H，rs 1061170）和LOC 387715/ARMS 2（A69 S，rs 10490924）基因的单核苷酸多态性进行了基因分型。作者进行了调整的非条件logistic回归分析，并评估了这些基因型之间的相互作用，以确定CFH和LOC 387715/ARMS 2基因型与抗氧化剂加锌治疗之间的关系。主要结果测量：遗传变异与治疗反应之间的相互作用，通过从高危到晚期AMD的进展来确定。876例患者中有264例从AREDS 3类（中度AMD）进展至4类或5类（分别为单侧或双侧晚期AMD），或从4类进展至5类。在CFH Y 402 H基因型和补充抗氧化剂加锌之间观察到治疗相互作用（CC; P = 0.03）。与不服用锌的组相比，在服用锌的AREDS治疗组中观察到相互作用（P = 0.004），但与不服用抗氧化剂的组相比，服用抗氧化剂的组中没有观察到相互作用（P = 0.59）。LOC 387715/ARMS 2没有观察到显著的治疗相互作用。结论：本研究的结果表明，个体对AREDS补充剂的反应可能与CFH基因型有关。这可能通过预测治疗结果和潜在地预防那些可能不受益的人的不必要的副作用而具有临床相关性。在考虑修改目前的管理之前，需要对这些分析进行确证。这是最早提出基因型和治疗之间相互作用的药物遗传学研究之一。
Objective: To determine if CFH and LOC387715/ARMS2 genotypes influence treatment response to AREDS-type nutritional supplementation with antioxidants and zinc.Design: Retrospective analysis of participants in a randomized, controlled clinical trial, the Age-Related Eye Disease Study (AREDS).Participants and/or Controls: Eight hundred seventy-six AREDS study participants who were considered at high risk for developing advanced age-related macular degeneration (AMD). Methods: Using DNA extracted from venous blood of 876 white participants in AREDS categories 3 and 4, that is, those considered to be at high risk for progression to advanced AMD, the authors genotyped for the single nucleotide polymorphisms in the CFH (Y402H, rs1061170) and LOC387715/ARMS2 (A69S, rs10490924) genes. The authors performed adjusted unconditional logistic regression analysis and assessed interactions of these genotypes to determine the relationship between CFH and LOC387715/ARMS2 genotype and treatment with antioxidants plus zinc.Main Outcome Measures: Interaction between genetic variants and treatment response as determined by progression from high-risk to advanced AMD.Results: Progression occurred in 264 of 876 patients from AREDS category 3 (intermediate AMD) to category 4 or 5 (unilateral or bilateral advanced AMD, respectively), or from category 4 to category 5. A treatment interaction was observed between the CFH Y402H genotype and supplementation with antioxidants plus zinc (CC; P = 0.03). An interaction (P = 0.004) was observed in the AREDS treatment groups taking zinc when compared with the groups taking no zinc, but not in groups taking antioxidants compared with those taking no antioxidants (P = 0.59). There were no significant treatment interactions observed with LOC387715/ARMS2.Conclusions: The findings of this study indicate that an individual's response to AREDS supplements may be related to CFH genotype. This could have clinical relevance by predicting treatment outcome and potentially preventing unwanted side effects in those who may not benefit. Corroboration of these analyses is needed before considering modification of current management. This is among the first pharmacogenetic studies to suggest interaction between genotype and treatment.