Survivors of traumatic injuries confront many difficulties in their struggle to recover. Rehabilitation efforts are undercut by many complications. While traumatic injuries are the leading cause of death for Americans under the age of 44, they also are a significant reason for rehabilitation services. A critical interruption of the recovery process after traumatic injury is the development of Adult Respiratory Distress Syndrome (ARDS) or Acute Lung Injury (ALl). The goal of this study is to identify genetic polymorphisms that predict risk of ARDS or ALl following trauma. In this study, we will focus on candidate genes for pulmonary function including those involved in nitric oxide production, vascular resistance, cellular responses to injury, cellular signaling, and alveolar function. We will fist determine whether individual polymorphisms predict risk of ARDS or All following trauma (Aim 1). We will then determine whether the relationships between individual polymorphisms and ARDS/ALI following trauma are dependent on environmental factors (Aim 2). Using a hierarchical systems approach, we will then determine whether the relationships between individual polymorphisms and ARDS/ALI following trauma are dependent on one or more other polymorphisms (Aim 3). Finally, we will use a hierarchical systems approach to determine whether the relationships between combinations of polymorphisms and ARDS/ALI following trauma are dependent on one or more environmental factors (Aim 4). This study will capitalize on local expertise and resources in trauma medicine, biochemical and molecular genetics, statistical genetics, and bioinformatics to provide a comprehensive approach to the identification of genetic predictors of trauma recovery and rehabilitation.
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