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首页> 外文期刊>BMC Medical Genomics >Microarray characterization of gene expression changes in blood during acute ethanol exposure
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Microarray characterization of gene expression changes in blood during acute ethanol exposure

机译：急性乙醇暴露期间血液中基因表达变化的微阵列表征

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Background As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we performed a DNA microarray analysis of human whole blood samples from a five-time point study of subjects administered ethanol orally, followed by breathalyzer analysis, to monitor blood alcohol concentration (BAC) to discover significant gene expression changes in response to the ethanol exposure. Methods Subjects were administered either orange juice or orange juice with ethanol. Blood samples were taken based on BAC and total RNA was isolated from PaxGene? blood tubes. The amplified cDNA was used in microarray and quantitative real-time polymerase chain reaction (RT-qPCR) analyses to evaluate differential gene expression. Microarray data was analyzed in a pipeline fashion to summarize and normalize and the results evaluated for relative expression across time points with multiple methods. Candidate genes showing distinctive expression patterns in response to ethanol were clustered by pattern and further analyzed for related function, pathway membership and common transcription factor binding within and across clusters. RT-qPCR was used with representative genes to confirm relative transcript levels across time to those detected in microarrays. Results Microarray analysis of samples representing 0%, 0.04%, 0.08%, return to 0.04%, and 0.02% wt/vol BAC showed that changes in gene expression could be detected across the time course. The expression changes were verified by qRT-PCR. The candidate genes of interest (GOI) identified from the microarray analysis and clustered by expression pattern across the five BAC points showed seven coordinately expressed groups. Analysis showed function-based networks, shared transcription factor binding sites and signaling pathways for members of the clusters. These include hematological functions, innate immunity and inflammation functions, metabolic functions expected of ethanol metabolism, and pancreatic and hepatic function. Five of the seven clusters showed links to the p38 MAPK pathway. Conclusions The results of this study provide a first look at changing gene expression patterns in human blood during an acute rise in blood ethanol concentration and its depletion because of metabolism and excretion, and demonstrate that it is possible to detect changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study serves as a workflow to investigate the biology linked to expression changes across a time course and from these changes, to identify target genes that could serve as biomarkers linked to pilot performance.
机译：背景作为确定乙醇对飞行性能的不利影响的民航安全计划的一部分，我们对五次点口服乙醇实验的受试者进行了人类全血样本的DNA微阵列分析，然后进行了呼吸分析仪分析，监测血液中的酒精浓度（BAC）以发现响应乙醇暴露的显着基因表达变化。方法对象被给予橙汁或橙汁与乙醇。基于BAC采集血样，并从PaxGene？中分离总RNA。血液管。扩增的cDNA用于微阵列和定量实时聚合酶链反应（RT-qPCR）分析，以评估差异基因表达。以流水线方式分析微阵列数据以总结和归一化，并使用多种方法评估结果在各个时间点的相对表达。候选基因在乙醇反应中表现出独特的表达模式，通过模式进行聚类，并进一步分析聚类内和跨聚类的相关功能，途径成员和常见转录因子结合。 RT-qPCR与代表性基因一起使用，以确认跨时间的相对转录水平与微阵列中检测到的水平相对。结果对代表0％，0.04％，0.08％，返回0.04％和0.02％wt / vol BAC的样品进行微阵列分析表明，可以在整个时间过程中检测到基因表达的变化。通过qRT-PCR验证表达变化。从微阵列分析中鉴定出来的感兴趣的候选基因（GOI），通过表达模式在五个BAC点上聚集在一起，显示了七个协同表达的组。分析显示了基于功能的网络，共享的转录因子结合位点和集群成员的信号通路。这些包括血液功能，先天免疫和炎症功能，乙醇代谢预期的代谢功能以及胰腺和肝功能。七个簇中的五个表明与p38 MAPK途径相关。结论这项研究的结果首次揭示了在血液中乙醇浓度急剧上升及其代谢和排泄引起的耗竭过程中人血液中基因表达模式的变化，并证明使用总RNA可以检测基因表达的变化从全血中分离出来。这项研究的分析方法是一种工作流程，用于研究与时间过程中表达变化相关的生物学行为，并根据这些变化确定目标基因，这些基因可作为与飞行员绩效相关的生物标记。

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