Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality
Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality
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DOI：
10.1089/ars.2018.7701
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发表时间：
2019-06-18
影响因子：
6.6
通讯作者：
Garcia, Joe G. N.
中科院分区：
文献类型：
--
作者：
Lynn, Heather;Sun, Xiaoguang;Garcia, Joe G. N.
最新进展：目前的ARDS定义依赖于未能涵盖疾病病理、严重程度和死亡风险的多样性的临床特征。我们对现有的ARDS文献进行了全面的调查，以确定与ARDS的易感性有关的基因和遗传变异(候选基因和有限的全基因组关联研究方法)，希望发现ARDS风险和死亡率的新生物标记物，以及潜在的新的ARDS治疗靶点。我们进一步试图解决在ARDS的易感性和死亡率方面存在的众所周知的健康差异。关键问题：生物信息学分析确定了201个ARDS候选基因，路径分析表明，在进化上保守的关键炎症途径中具有很强的优势，包括活性氧物种、先天免疫相关炎症和内皮血管信号通路。未来方向：采用结合临床特征、基因组学、转录组学和蛋白质组学的系统生物学方法的未来研究可能允许更好地定义生物相关的途径和基因-表型联系，并通过分子签名改进不同ARDS患者的亚型分型策略。这些努力应该会促进ARDS临床试验的成功，并对ARDS的病理生物学有更好的基础了解。
Recent Advances: The current ARDS definition relies on clinical characteristics that fail to capture the diversity of disease pathology, severity, and mortality risk. We undertook a comprehensive survey of the available ARDS literature to identify genes and genetic variants (candidate gene and limited genome-wide association study approaches) implicated in susceptibility to developing ARDS in hopes of uncovering novel biomarkers for ARDS risk and mortality and potentially novel therapeutic targets in ARDS. We further attempted to address the well-known health disparities that exist in susceptibility to and mortality from ARDS. Critical Issues: Bioinformatic analyses identified 201 ARDS candidate genes with pathway analysis indicating a strong predominance in key evolutionarily conserved inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation, and endothelial vascular signaling pathways. Future Directions: Future studies employing a system biology approach that combines clinical characteristics, genomics, transcriptomics, and proteomics may allow for a better definition of biologically relevant pathways and genotype-phenotype connections and result in improved strategies for the sub-phenotyping of diverse ARDS patients via molecular signatures. These efforts should facilitate the potential for successful clinical trials in ARDS and yield a better fundamental understanding of ARDS pathobiology.