University of Illinois, Chicago, IL 60612, USA.
Proc Am Thorac Soc. 2011 May;8(2):167-72. doi: 10.1513/pats.201101-002MS.
Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome, are complex illnesses involving the interplay of both environmental (such as mechanical ventilation) and genetic factors. To understand better the underlying mechanisms of pathogenesis associated with ALI, we recently identified several candidate genes by global expression profiling in preclinical models of ALI and relevant single-nucleotide polymorphisms. We summarize here several strategies successfully used to identify novel ALI candidate genes and detail the validation of variants in these genes as contributing factors to ALI pathobiology, conclusions based on functional analyses, and specific genetic association studies conducted in ALI cohorts. Continued insights into ALI pathogenesis and identification of genetic variants, which confer ALI risk and severity, promise to reveal novel molecular therapeutic targets that can be translated into personalized treatments to reduce the very high, unacceptable mortality of this disorder.
急性肺损伤（ALI）及其更严重的形式，急性呼吸窘迫综合征，是一种复杂的疾病，涉及环境（如机械通气）和遗传因素的相互作用。为了更好地理解与 ALI 相关的发病机制的潜在机制，我们最近通过 ALI 临床前模型的全基因组表达谱分析确定了几个候选基因和相关的单核苷酸多态性。我们在这里总结了几种成功用于鉴定新型 ALI 候选基因的策略，并详细说明了这些基因中的变异作为 ALI 病理生物学的致病因素的验证，基于功能分析的结论，以及在 ALI 队列中进行的特定遗传关联研究。对 ALI 发病机制的持续深入了解以及鉴定出与 ALI 风险和严重程度相关的遗传变异，有望揭示新的分子治疗靶点，从而转化为个性化治疗，以降低这种疾病极高、不可接受的死亡率。
