Department of Biostatistics Epidemiology and Scientific Computing, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Invest Ophthalmol Vis Sci. 2012 Aug 27;53(9):5899-904. doi: 10.1167/iovs.12-9634.
To identify differentially expressed genes and to elucidate gene interaction networks and molecular pathways possibly contributing to the development of POAG.
Genome-wide expression profiling experiments were carried out using ABI high-density oligonucleotide microarrays in leukocytes from 25 POAG patients and 12 age-, ethnicity-, and sex-matched normal controls. Significantly modulated genes were defined as those with a false discovery rate (FDR) <0.01 and an absolute fold change (FC) >1.5. These genes are then mapped to relevant biologic processes and pathways.
We identified 563 genes that were significantly dysregulated (410 upregulated and 153 downregulated) in POAG compared with normal controls ("POAG gene signature"). These genes were significantly enriched with functions related to, among others, nucleoside, nucleotide, and nucleic acid metabolism, the mitogen-activated protein kinase kinase kinase cascade, apoptosis, protein synthesis, cell cycle, intracellular signaling cascade, and nervous system development and function. Among the most significantly altered canonical pathways in POAG were the ephrin receptor signaling, ubiquitin proteasome pathway, hypoxia signaling, neuregulin, and G-protein coupled receptor signaling. Network analysis revealed potentially critical roles of UBE2, TBP, GNAQ, SUMO1, CREB, p70S6k, IFNG, and CaMKII that are interacting with NF-κB, ubiquitin, proteasome, PI3K/AKT, IL12, and PDGF in the disease pathogenesis.
Our study revealed blood gene signatures that clearly distinguish POAG patients and normal controls, as well as altered pathways that may shed light on POAG pathogenesis.
鉴定差异表达基因，并阐明可能导致 POAG 发生的基因相互作用网络和分子途径。
使用 ABI 高密度寡核苷酸微阵列在 25 名 POAG 患者和 12 名年龄、种族和性别匹配的正常对照者的白细胞中进行全基因组表达谱实验。将 FDR<0.01 且绝对倍数变化 (FC)>1.5 的显著调节基因定义为差异表达基因。这些基因随后被映射到相关的生物学过程和途径。
我们确定了 563 个在 POAG 中显著失调的基因（410 个上调，153 个下调）与正常对照组相比（“POAG 基因特征”）。这些基因显著富集与核苷、核苷酸和核酸代谢、丝裂原活化蛋白激酶激酶激酶级联、细胞凋亡、蛋白质合成、细胞周期、细胞内信号级联和神经系统发育和功能等功能相关。在 POAG 中最显著改变的经典途径包括 Ephrin 受体信号、泛素蛋白酶体途径、缺氧信号、神经调节素和 G 蛋白偶联受体信号。网络分析显示，UBE2、TBP、GNAQ、SUMO1、CREB、p70S6k、IFNG 和 CaMKII 等基因与 NF-κB、泛素、蛋白酶体、PI3K/AKT、IL12 和 PDGF 相互作用，在疾病发病机制中可能发挥关键作用。
我们的研究揭示了能够明确区分 POAG 患者和正常对照者的血液基因特征，以及可能阐明 POAG 发病机制的改变途径。
