人类血浆代谢组学研究贯穿年龄相关性黄斑变性的所有阶段，确定潜在的脂质生物标志物。
Human Plasma Metabolomics Study across All Stages of Age-Related Macular Degeneration Identifies Potential Lipid Biomarkers.
机构信息
Retina Service, Massachusetts Eye and Ear, Harvard Ophthalmology AMD Center of Excellence, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Association for Innovation and Biomedical Research on Light, Association for Innovation and Biomedical Research on Light and Image (AIBILI), Coimbra, Portugal; Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Systems Genetics and Genomics Unit, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
出版信息
Ophthalmology. 2018 Feb;125(2):245-254. doi: 10.1016/j.ophtha.2017.08.008. Epub 2017 Sep 12.
PURPOSE
To characterize the plasma metabolomic profile of patients with age-related macular degeneration (AMD) using mass spectrometry (MS).
DESIGN
Cross-sectional observational study.
PARTICIPANTS
We prospectively recruited participants with a diagnosis of AMD and a control group (>50 years of age) without any vitreoretinal disease.
METHODS
All participants underwent color fundus photography, used for AMD diagnosis and staging, according to the Age-Related Eye Disease Study classification scheme. Fasting blood samples were collected and plasma was analyzed by Metabolon, Inc. (Durham, NC), using ultrahigh-performance liquid chromatography (UPLC) and high-resolution MS. Metabolon's hardware and software were used to identify peaks and control quality. Principal component analysis and multivariate regression were performed to assess differences in the metabolomic profiles of AMD patients versus controls, while controlling for potential confounders. For biological interpretation, pathway enrichment analysis of significant metabolites was performed using MetaboAnalyst.
MAIN OUTCOME MEASURES
The primary outcome measures were levels of plasma metabolites in participants with AMD compared with controls and among different AMD severity stages.
RESULTS
We included 90 participants with AMD (30 with early AMD, 30 with intermediate AMD, and 30 with late AMD) and 30 controls. Using UPLC and MS, 878 biochemicals were identified. Multivariate logistic regression identified 87 metabolites with levels that differed significantly between AMD patients and controls. Most of these metabolites (82.8%; n = 72), including the most significant metabolites, belonged to the lipid pathways. Analysis of variance revealed that of the 87 metabolites, 48 (55.2%) also were significantly different across the different stages of AMD. A significant enrichment of the glycerophospholipids pathway was identified (P = 4.7 × 10) among these metabolites.
CONCLUSIONS
Participants with AMD have altered plasma metabolomic profiles compared with controls. Our data suggest that the most significant metabolites map to the glycerophospholipid pathway. These findings have the potential to improve our understanding of AMD pathogenesis, to support the development of plasma-based metabolomics biomarkers of AMD, and to identify novel targets for treatment of this blinding disease.
目的
使用质谱（MS）分析与年龄相关的黄斑变性（AMD）患者的血浆代谢组特征。
设计
横断面观察性研究。
参与者
我们前瞻性招募了 AMD 诊断患者和无任何玻璃体视网膜疾病的对照组（>50 岁）参与者。
方法
所有参与者均接受了彩色眼底照相检查，根据年龄相关性眼病研究分类方案对 AMD 进行诊断和分期。采集空腹血样，由 Metabolon, Inc.（北卡罗来纳州达勒姆）使用超高效液相色谱（UPLC）和高分辨率 MS 进行分析。Metabolon 的硬件和软件用于识别峰和控制质量。为了评估 AMD 患者与对照组之间代谢组特征的差异，同时控制潜在的混杂因素，我们进行了主成分分析和多元回归。为了进行生物学解释，使用 MetaboAnalyst 对有意义的代谢物进行途径富集分析。
主要观察指标
主要观察指标是 AMD 患者与对照组参与者的血浆代谢物水平以及不同 AMD 严重程度阶段的水平。
结果
我们纳入了 90 名 AMD 患者（早期 AMD 30 名，中期 AMD 30 名，晚期 AMD 30 名）和 30 名对照者。使用 UPLC 和 MS 鉴定了 878 种生化物质。多元逻辑回归确定了 87 种代谢物的水平在 AMD 患者和对照组之间存在显著差异。这些代谢物中的大多数（82.8%；n=72），包括最显著的代谢物，属于脂质途径。方差分析显示，在 87 种代谢物中，有 48 种（55.2%）在 AMD 的不同阶段也存在显著差异。在这些代谢物中，甘油磷脂途径显著富集（P=4.7×10）。
结论
与对照组相比，AMD 患者的血浆代谢组特征发生改变。我们的数据表明，最显著的代谢物映射到甘油磷脂途径。这些发现有可能提高我们对 AMD 发病机制的理解，支持开发基于血浆的 AMD 代谢组学生物标志物，并确定治疗这种致盲疾病的新靶点。
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