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Investigating the role of the R213G SOD3 polymorphism in lung disease

研究 R213G SOD3 多态性在肺部疾病中的作用

基本信息

批准号：
8656652
负责人：
RUSSELL Paul BOWLER
金额：
$ 29.62万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8656652
关键词：
Acute Affect Amino Acids Animal Model Antioxidants Apoptotic Arginine Attenuated Base Pairing Binding Biological Assay Breathing Candidate Disease Gene Cardiovascular Diseases Cause of Death Cells Chronic Obstructive Airway Disease Cigarette Code Confocal Microscopy Cytosine Data Development Diagnostic tests Elements Epithelial Epithelium Excision Extracellular Fluid Extracellular Matrix Extracellular Space Functional RNA Gene Proteins Genes Genetic Polymorphism Genetic Predisposition to Disease Glycine Goals Guanine Hereditary Disease Heritability Human Human Genetics In Vitro Inflammation Injury Knock-in Mouse Knock-out Knockout Mice Knowledge Laboratories Lead Length of Stay Lipopolysaccharides Liquid substance Lung Lung diseases Macrophage Activation Mass Spectrum Analysis Methods Mus Myocardial Infarction Nitric Oxide Observational Study Organ Oxidants Oxidative Stress Plasma Population Predisposition Protein Binding Proteins Pulmonary Emphysema Pulmonary Function Test/Forced Expiratory Volume 1 Reporting Resolution Resources Respiratory physiology Risk Risk Factors Role Signal Pathway Single Nucleotide Polymorphism Smoke Smoker Smoking Stroke Structure of parenchyma of lung Superoxide Dismutase Testing Time Tissues Tobacco smoke Toxin United States Variant Western Blotting antioxidant therapy biobank cigarette smoking cytokine experience extracellular genetic variant human DNA in vivo lung injury macrophage novel diagnostics overexpression prevent protein distribution protein function research study response

项目摘要

The rs1799895 single nucleotide polymorphism (SNP) is a non-synonymous base pair change in SOD3 that results in an arginine-to-glycine substitution (R213G) in extracellular superoxide dismutase protein (EC-SOD). This region is responsible for EC- SODs binding to extracellular matrix increases plasma levels 10-fold. The R213G SNP protects smokers from developing chronic obstructive pulmonary disease (COPD) and acute exacerbations of COPD. The goal of this proposal is to elucidate the mechanism by which the R213G protects the lung from tobacco smoke. To accomplish this aim, we have created a knock-in mouse with the identical SNP. Our methods will utilize more than a decade of experience studying the EC-SOD gene and COPD.

rs 1799895单核苷酸多态性（SNP）是一种非同义碱基对， SOD 3的变化导致甘氨酸取代为甘氨酸（R213 G），胞外超氧化物歧化酶蛋白（EC-SOD）。该地区负责欧盟- SOD与细胞外基质的结合使血浆水平增加10倍。R213G SNP 防止吸烟者患上慢性阻塞性肺疾病（COPD）， COPD急性加重。本提案的目的是阐明 R213 G可以保护肺部免受烟草烟雾的侵害。为了实现这一目标，我们创造了一个基因敲入的小鼠，我们的方法将利用更多研究EC-SOD基因和COPD的十多年经验。