Oxidative Stress Related Gene Polymorphisms in Acute kidney Injury

急性肾损伤氧化应激相关基因多态性

• 批准号: 8056099
• 负责人: MARY C PERIANAYAGAM
• 金额: $ 12.59万
• 依托单位: GENESYS RESEARCH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-20 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056099
• 关键词: 3-nitrotyrosine; Accounting; Acute; Acute Renal Failure with Renal Papillary Necrosis; Advisory Committees; Affect; Age; Antioxidants; Biological Markers; Caring; Cessation of life; Classification; Clinical; Clinical Data; Complex; Complication; Creatinine; Data; Dialysis procedure; Disease; Disease Outcome; Distress; Enzymes; Epidemiology; Equilibrium; Etiology; Frequencies; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; Health; High Prevalence; Hospital Costs; Hospital Mortality; Hospitalization; Hospitals; Hypochlorous Acid; Incidence; Individual; Inflammatory Response; Injury; Interleukin-10; Investigation; Kidney; Kidney Diseases; Laboratories; Length of Stay; Measures; Mediating; Mentors; Morbidity - disease rate; NADP; Organ; Outcome; Outcome Measure; Oxidants; Oxidases; Oxidative Stress; Pathogenesis; Patients; Peroxidases; Plasma; Play; Population; Postoperative Period; Predisposition; Principal Investigator; Production; Public Health; Reactive Oxygen Species; Recruitment Activity; Regulation; Renal function; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Serum; Severities; Severity of illness; Single Nucleotide Polymorphism; Site; Staging; Tissues; Training Programs; Translational Research; Tubular formation; Tumor Necrosis Factor-alpha; Whole Blood; Wound Healing; adverse outcome; base; catalase; cohort; design; epidemiology study; experience; genetic epidemiology; genetic profiling; genetic variant; glutathione peroxidase; human CYBA protein; insight; leukocyte activation; monocyte; mortality; neutrophil; novel; population based; skills; urinary

DESCRIPTION (provided by applicant): Acute kidney injury (AKI) is a complex disorder with an incidence of 5-10%, and mortality exceeding 50% among those who require dialysis. Oxidative stress, an imbalance between pro- and anti-oxidants, plays a pivotal role in the host inflammatory responses that mediate the severity of AKI. Yet, the importance of susceptibility genetic factors that influence the extent of oxidative stress has remained largely unexplored. The principal investigator (PI) has designed a rigorous training program that will provide the necessary skills, experience, and opportunities to develop into an independent investigator in the field of translational research and genetic epidemiology for the study of AKI. The PI will attend key didactic courses, and carry out an original research from it inception to completion. Mentors and advisory committee have extensive experience in clinical, translational and laboratory investigation of AKI. There are several well-characterized and functionally-relevant single nucleotide polymorphisms (SNPs) of genes encoding pro-oxidant enzymes that promote tissue injury, namely NADPH oxidase (p22phox) and myeloperoxidase (MPO), and anti-oxidant enzymes that promote tissue repair, namely catalase and glutathione peroxidase-1 (GPx-1). These genetic variants might influence the extent of oxidative stress. The hypotheses to be investigated are whether polymorphisms in these oxidative stress-related genes predetermine severity of AKI, and are independent risk factors for adverse clinical outcomes. The specific aims are to: 1) Characterize the frequency of these pro- and anti-oxidant genetic variants in a large cohort of patients with AKI; 2) Examine their relationship to circulating biomarkers of oxidative stress, and measures of renal disease severity; and 3) Evaluate whether these genetic markers individually or in combinations, predict adverse clinical outcomes, namely dialysis requirement and in-hospital mortality. The study will also identify common haplotypes within the gene locus using appropriate tag-SNPs. This project is achievable and promises to provide new insights into the importance of genetic markers as novel susceptibility factors for disease severity in AKI. The results may help identify patients who may benefit from anti-oxidants, on the basis of the identified genetic profiles. PUBLIC HEALTH RELEVANCE: Acute kidney injury (AKI) is a sudden loss of kidney function that is commonly seen in people who are in the hospital. Although AKI usually gets better on its own, some people are more likely to experience serious problems while in the hospital. This study will examine whether certain genes can help identify people with AKI who are more likely to experience more serious kidney and other health problems.

描述（由申请人提供）：