RAGE基因标签单核甘酸多态性（-429T/C）与严重创伤并发症的临床关联及功能研究

项目名称： RAGE基因标签单核甘酸多态性（-429T/C）与严重创伤并发症的临床关联及功能研究

项目编号： No.81201462

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 曾灵

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： 脓毒症和多器官功能衰竭（MODS）是创伤后的严重并发症，对它们的机制研究对大幅降低危重患者并发症有重要意义。糖基化终末产物受体（RAGE）是近年来发现的具有重要警报素受体分子，已发现其单核基因多态性（SNP）与多种感染性疾病密切相关，但与脓毒症易感性关系尚无研究。基于RAGE与严重创伤后并发症的密切关系，我们对RAGE基因进行了连锁不平衡分析，并在此基础上筛选出其整个基因的标签SNP-63bp ins/del，rs1800625,rs1800624和rs2070600。我们采用232名严重创伤患者DNA样本，对这4个标签SNP进行了基因分型和临床关联分析，发现rs1800625(-429 T／C)是一个与脓毒症和MODS密切相关的位点。因此，我们推测-429T/C是一个有功能意义的，可能影响了RAGE基因启动子活性的SNP，并拟扩大在全国多中心收集的样本中对其进行关联和功能研究。

中文关键词： 创伤；糖基化终末产物受体；脓毒症；多器官功能衰竭；单核苷酸多态性

英文摘要： Sepsis and multiple organ dysfunction syndrome (MODS) are shown to be common and severe complications in trauma patients. Therefore, preventing sepsis and MODS is crucial in the treatment of surviving patients with major trauma. Increasing evidence suggests that genetic variants, particularly single nucleotide polymorphisms (SNPs), are critical determinants for inter-individual differences in both inflammatory responses and clinical outcome in trauma patients. Delineating the variation in genes and associated differences in response to trauma might contribute to the development of new genetically tailored diagnostic and therapeutic interventions that will improve outcome in the patients with major trauma.The receptor for advanced glycation end products (RAGE), has been recognized as a multiligand receptor, specially playing a pivotal roles in innate immune responses as a pattern-recognition receptor (PRR) in sensing both "pathogen-associated molecular patterns" (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). RAGE gene polymorphism have been associated with a variety of inflammation-related dieases, but the impact of RAGE gene polymorphism on the outcome of critical ill patients remains to be unidentified. Among the four tag SNPs of the RAGE gene（63bp ins/del，rs1800625，rs1800624 and rs2070600

英文关键词： trauma；the receptor for advanced glycation of end product；sepsis；multiple organ dysfunction sydrome；single nucleotide polymorphism