U.S. Army Institute of Surgical Research, Fort Sam Houston, TX 78234, USA.
Curr Genomics. 2011 Sep;12(6):428-42. doi: 10.2174/138920211797248574.
Severe hemorrhage due to trauma is a major cause of death throughout the world. It has often been observed that some victims are able to withstand hemorrhage better than others. For decades investigators have attempted to identify physiological mechanisms that distinguish survivors from nonsurvivors for the purpose of providing more informed therapies. As an alternative approach to address this issue, we have initiated a research program to identify genes and genetic mechanisms that contribute to this phenotype of survival time after controlled hemorrhage. From physiogenomic studies using inbred rat strains, we have demonstrated that this phenotype is a heritable quantitative trait, and is therefore a complex trait regulated by multiple genes. Our work continues to identify quantitative trait loci as well as potential epigenetic mechanisms that might influence survival time after severe hemorrhage. Our ultimate goal is to improve survival to traumatic hemorrhage and attendant shock via regulation of genetic mechanisms and to provide knowledge that will lead to genetically-informed personalized treatments.
创伤导致的严重出血是全世界死亡的主要原因。人们经常观察到，一些受害者比其他人更能耐受出血。几十年来，研究人员一直试图确定能够区分幸存者和非幸存者的生理机制，以便提供更有针对性的治疗方法。作为解决这个问题的另一种方法，我们已经启动了一个研究项目，以确定导致这种在控制出血后存活时间的表型的基因和遗传机制。通过使用近交系大鼠进行生理基因组学研究，我们已经证明这种表型是一种可遗传的数量性状，因此是一种由多个基因调控的复杂性状。我们的工作仍在继续确定数量性状基因座以及可能影响严重出血后存活时间的潜在表观遗传机制。我们的最终目标是通过调节遗传机制来提高创伤性出血和伴随性休克的存活率，并提供有助于实现基于基因的个体化治疗的知识。
