Genetic predisposition to pathologic inflammation in trauma patients with respect to the ISS based on data from cooperating centers

在德国，创伤在死亡原因、急性疾病的治疗费用、长期死亡率和随后的经济成本中占有相关份额。根据创伤的严重程度，创伤后患者会出现全身性炎症反应综合征(SIRS)，这决定了患者的个人临床病程。到目前为止，对负责任的(细胞内)调控机制的了解仍然有限。虽然联合项目中的各种研究侧重于选定候选基因的全球表达模式和基因分型，但该项目的目的是基于流行病学方法研究家族易感性。为了充分规划和启动流行病学研究，将在本项目的第一部分获得关于促进创伤性炎症反应的危险因素的知识。将对创伤登记中选定的数据(由德国创伤学会提供)进行系统分析，以便发现影响变量并进行分组分析。同时，将开发一份问卷来量化患者一级亲属的病理免疫反应，并在一项试点研究中进行评估。在规划下一项病例对照研究时，需要将这些参数作为潜在的风险因素加以考虑。在这项研究中，创伤患者的前瞻性数据将从合作中心收集。患者将被定义为病例或对照，取决于他们的结果(多器官衰竭)。病理性免疫反应模式的家族史(伤口愈合障碍、败血症倾向、多器官衰竭等)将分别在病例和对照中进行研究和比较。

In Germany, trauma has a relevant share in the causes of death, the costs of therapy for acute illness, long-term mortality and subsequent economic costs. Depending on the severity of the trauma, posttraumatic patients develop a systemic inflammatory response syndrome (SIRS), which decisively determines the individual clinical course of the patient. So far, the understanding of the responsible (intra-)cellular regulatory mechanisms remains limited. While various studies within the joint project focus on global patterns of expression and genotyping of chosen candidate genes, the aim of this project is to study familial predisposition based on an epidemiological approach. In order to plan and initiate an epidemiological study adequately, knowledge on risk factors promoting traumatic inflammatory response will be gained during the first part of this project. Selected data from the trauma registry (provided by the German Trauma Society) will be systematically analysed in order to detect influencing variables and to perform subgroup analyses. Parallel to this, a questionnaire to quantify pathologic immune response in first degree relatives of patients shall be developed and evaluated in a pilot study. These parameters need to be taken into account as potential risk factors in the planning of a following case-control study. In this study prospective data on trauma patients will be collected from cooperating centers. Patients will be defined as cases or controls depending on their outcome (multiple organ failure). Family history of pathologic immune response patterns (wound healing disorder, disposition to sepsis, multiple organ failure, etc.) will be studied and compared in cases and controls, respectively.