Genetic Polymorphisms in Pediatric Lung Injury

小儿肺损伤的基因多态性

• 批准号: 6910788
• 负责人: MICHAEL W QUASNEY
• 金额: $ 18.1万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2006-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6910788
• 关键词: CD95 molecule; adult respiratory distress syndrome; cell adhesion molecules; children; clinical research; genetic markers; genetic polymorphism; genetic screening; genetic susceptibility; genotype; haploidy; human subject; inflammation; interleukin 8; lung injury; pathologic process; patient oriented research; peptidyl dipeptidase A; pneumonia; respiratory insufficiency /failure; single nucleotide polymorphism; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): The objective of this proposal is to further understand the pathogenesis of acute respiratory failure in children with community-acquired pneumonia (CAP). The central hypothesis is that the continuum of CAP-induced lung injury, from minimal lung injury to severe respiratory failure and acute respiratory distress syndrome (ARDS), represents, in part, an imbalance between pro-inflammatory/pro-fibrotic and anti-inflammatory/antifibrotic mediators, and that this imbalance is in part influenced by genetic determinants. Support for this proposal will be used to examine and analyze pilot data in order to determine if specific genetic polymorphisms are associated with the clinical presentation of, or outcome from, CAP-induced lung injury and respiratory failure in children. The project will seek evidence of genetic markers (SNPs) that can be utilized to predict children with CAP that are at high risk for poor outcomes and may benefit from earlier or more aggressive intervention. The pilot data obtained from this project will be used to plan for a study of a larger prospective, multi-institutional cohort. To test our hypothesis, the specific aims of this proposal are as follows: To test the prediction that known single nucleotide polymorphisms (SNPs) in genes involving inflammation, specifically TNF-alpha, IL-8, ICAM-1, Fas, and ACE, are associated with CAP-induced severe lung injury and respiratory failure in children. To test the prediction that specific SNP haplotypes in the TNF-alpha and/or Fas gene loci are associated with CAP-induced severe lung injury and respiratory failure in children. This proposal will utilize a multi-disciplinary approach to analyze and compare frequencies of specific genetic polymorphisms in children with varying degrees of CAP-induced lung injury and respiratory failure. The research team will include investigators trained in Pediatric Critical Care, Infectious Diseases, Molecular Sciences, and Epidemiology. The strengths of this proposal include access to large populations of children with CAP, the track record of the investigators in polymorphic analysis, particularly in patients with CAP, and the commitment of the participating institution to provide state-of-the-art technologies to the investigators.

描述(申请人提供)：这项建议的目的是为了进一步了解社区获得性肺炎(CAP)儿童急性呼吸衰竭的发病机制。中心假设是，CAP诱导的肺损伤的连续体，从轻微的肺损伤到严重的呼吸衰竭和急性呼吸窘迫综合征(ARDS)，部分代表了促炎/促纤维化和抗炎/抗纤维化介质之间的失衡，这种失衡在一定程度上受到遗传决定因素的影响。对这项提议的支持将用于检查和分析试点数据，以确定特定的基因多态是否与儿童CAP诱导的肺损伤和呼吸衰竭的临床表现或结果相关。该项目将寻找遗传标记(SNPs)的证据，这些SNPs可用于预测患有CAP的儿童，这些儿童具有不良结局的高风险，并可能受益于更早或更积极的干预。从该项目获得的试点数据将用于规划对更大规模的预期多机构队列的研究。为了验证我们的假设，这项建议的具体目的如下：测试炎症相关基因，特别是肿瘤坏死因子-α、IL-8、ICAM-1、Fas和ACE的已知单核苷酸多态(SNPs)与CAP引起的儿童严重肺损伤和呼吸衰竭的预测。目的：验证肿瘤坏死因子-α和/或Fas基因座上特定的SNP单倍型与CAP所致儿童严重肺损伤和呼吸衰竭的相关性。这项建议将利用多学科方法来分析和比较不同程度CAP诱导的肺损伤和呼吸衰竭儿童的特定基因多态频率。研究小组将包括接受过儿科危重护理、传染病、分子科学和流行病学培训的研究人员。这一提议的优势包括接触到大量患有CAP的儿童，调查人员在多态分析方面的记录，特别是在CAP患者中，以及参与机构承诺向调查人员提供最先进的技术。