Metabolome-Wide Association Study of Primary Open Angle Glaucoma
Metabolome-Wide Association Study of Primary Open Angle Glaucoma
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DOI：
10.1167/iovs.15-16702
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发表时间：
2015-07-01
影响因子：
4.4
通讯作者：
Brantley, Milam A., Jr.
中科院分区：
文献类型：
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作者：
Burgess, L. Goodwin;Uppal, Karan;Brantley, Milam A., Jr.
目的。目的：探讨原发性开角型青光眼（POAG）患者是否可以根据代谢特征与对照组进行区分。我们使用超高分辨率质谱- C18液相色谱对72例POAG患者和72例对照者的冷冻血浆样本进行代谢组学分析。采用全代谢组Spearman相关性选择与POAG相关的差异表达代谢物（DEM）。我们使用Benjamini和Hochberg错误发现率（FDR）校正多重检验的P值。采用层次聚类分析（HCA）描述参与者与DEM之间的关系。差异表达的代谢物与METLIN代谢组学数据库匹配；使用MetaboAnalyst分析DEM和与DEM显著相关的代谢物，以确定poag中改变的代谢途径。在过滤后恢复的2440 m/z（质量/电荷）特征中，在FDR = 0.05时，POAG病例与对照组之间有41个差异。分层聚类分析表明，这些DEM可关联成8个聚类；其中三个簇包含了大部分的DEM，包括棕榈酰肉碱、羟基麦角钙化醇，以及与鞘脂、其他维生素d相关代谢物和萜烯匹配的高分辨率METLIN。代谢分析还显示类固醇生物合成途径可能发生改变。全球超高分辨率代谢组学强调了POAG中脂质代谢改变的重要性。结果表明，特定的代谢过程，如涉及棕榈酰肉碱、鞘脂、维生素d相关化合物和类固醇前体的代谢过程，可能与POAG状态有关，值得用有针对性的方法进行更详细的研究。
PURPOSE. To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics.METHODS. We used ultra-high resolution mass spectrometry with C18 liquid chromatography for metabolomic analysis on frozen plasma samples from 72 POAG patients and 72 controls. Metabolome-wide Spearman correlation was performed to select differentially expressed metabolites (DEM) correlated with POAG. We corrected P values for multiple testing using Benjamini and Hochberg false discovery rate (FDR). Hierarchical cluster analysis (HCA) was used to depict the relationship between participants and DEM. Differentially expressed metabolites were matched to the METLIN metabolomics database; both DEM and metabolites significantly correlating with DEM were analyzed using MetaboAnalyst to identify metabolic pathways altered in POAG.RESULTS. Of the 2440 m/z (mass/charge) features recovered after filtering, 41 differed between POAG cases and controls at FDR = 0.05. Hierarchical cluster analysis revealed these DEM to associate into eight clusters; three of these clusters contained the majority of the DEM and included palmitoylcarnitine, hydroxyergocalciferol, and high-resolution METLIN matches to sphingolipids, other vitamin D-related metabolites, and terpenes. MetaboAnalyst also indicated likely alteration in steroid biosynthesis pathways.CONCLUSIONS. Global ultrahigh resolution metabolomics emphasized the importance of altered lipid metabolism in POAG. The results suggest specific metabolic processes, such as those involving palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors, may contribute to POAG status and merit more detailed study with targeted methods.