Oxidant Stress and Gene Polymorphisms in Bronchopulmonary Dysplasia

支气管肺发育不良的氧化应激和基因多态性

• 批准号: 8450789
• 负责人: Karen K Mestan
• 金额: $ 13.45万
• 依托单位: LURIE CHILDREN'S HOSPITAL OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8450789
• 关键词: 8-hydroxy-2' -deoxyguanosine; Address; Admixture; Affect; Antioxidants; Award; Biochemical; Biochemical Markers; Biological Assay; Biological Markers; Birth; Birthing Centers; Boston; Bronchopulmonary Dysplasia; Candidate Disease Gene; Chronic lung disease; Clinical; Clinical Research; Commit; Complex; Data; Development; Development Plans; Disease; Early identification; Enzymes; Epidemiologic Studies; Epidemiology; Ethnic Origin; Family; Foundations; Future; Gender; Genes; Genetic Markers; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Gestational Age; Glutathione S-Transferase; Goals; Hospitals; Incidence; Individual; Infant; Intervention; Laboratories; Lead; Life; Link; Literature; Lung diseases; Measures; Medical center; Mentors; Mentorship; Molecular Genetics; Morbidity - disease rate; Neonatal; Newborn Infant; Outcome; Pathogenesis; Pathway interactions; Patients; Pattern; Population; Predisposition; Premature Birth; Premature Infant; Prevention; Prevention strategy; Records; Regulation; Reporting; Research; Research Infrastructure; Research Personnel; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Severities; Single Nucleotide Polymorphism; Site; Societies; Solid; Stratification; Superoxide Dismutase; Susceptibility Gene; Techniques; Testing; Training; Translational Research; Umbilical Cord Blood; base; career development; case control; cohort; cost; design; experience; extracellular; genetic analysis; genetic association; genetic variant; high risk infant; improved; infancy; innovation; isoprostaglandin F2alpha type-III; mortality; novel; oxidant stress; patient oriented research; postnatal; prenatal; programs; skills; translational study; urinary

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy and is associated with significant morbidity, mortality and cost. Its pathogenesis remains poorly understood and predictors of the disease remain to be identified. Dr. Mestan is committed to elucidating the mechanisms that lead to BPD so that preventive strategies could be developed to decrease its incidence. Her short term goal is to investigate the epidemiologic associations of BPD with biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine (8- OHdG)) and gene polymorphisms implicated in pathways of oxidant stress, under the primary mentorship of Dr. Xiaobin Wang. This award would allow Dr. Mestan to gain the necessary skills to develop her research program and become an independent investigator. Her career development plan involves a multi-disciplinary program of didactic training and closely mentored molecular and genetic epidemiological research experiences. Her central hypothesis is that peripartum and postnatal oxidant stress, as measured by cord blood and urinary 8-isoprostane and 8-OHdG, and specific gene polymorphisms can independently or interactively affect the development of BPD. Her proposed study will employ the resources of two birth centers: The Boston Medical Center (BMC) birth cohort was established by Dr. Wang and colleagues in 1998, and is one of the largest ongoing birth cohorts in the U.S.; The Northwestern Memorial Hospital (NMH) cohort was initiated locally by Dr. Mestan in 2006, and will be developed further under the guidance of her mentors. Using a 1:2 case-control design of 1,200 preterm infants, she will investigate the following Specific Aims: 1) To identify relationships between cord blood and urinary biomarkers of oxidant stress and the development of BPD; and 2) To assess genetic associations of promising candidate genes (GSTP1, SOD3) with the risk of BPD, with adjustment for important clinical variables, population admixture, and multiple testing. Upon completion of this project, Dr. Mestan will have acquired essential experience in biochemical assay and genotyping techniques, and advanced statistical and genetic analyses, for the design and conduction of future studies of BPD and its outcomes.

支气管肺发育不良（BPD）是婴儿最常见的慢性肺部疾病，与显著的发病率、死亡率和成本相关。其发病机制仍知之甚少，疾病的预测因素仍有待确定。Mestan博士致力于阐明导致BPD的机制，以便制定预防策略以降低其发病率。她的短期目标是在王晓斌博士的主要指导下，研究BPD与生物标志物（8-异前列腺素和8-羟基脱氧鸟苷（8- OHdG））和与氧化应激途径相关的基因多态性之间的流行病学关联。该奖项将使梅斯坦博士获得必要的技能来发展她的研究项目，并成为一名独立的研究者。她的职业发展计划包括一个多学科的教学培训计划和密切指导的分子和遗传流行病学研究经验。她的中心假设是围产期和产后氧化应激（通过脐带血和尿8-异前列腺素和8-OHdG测量）以及特定的基因多态性可以独立或相互作用地影响BPD的发展。她提出的研究将利用两个生育中心的资源：波士顿医疗中心（BMC）出生队列由王博士及其同事于1998年建立，是美国最大的正在进行的出生队列之一；西北纪念医院（NMH）队列由Mestan博士于2006年在当地发起，并将在她的导师的指导下进一步发展。采用1:2的早产儿病例对照设计，她将研究以下具体目的：1)确定脐带血和尿液氧化应激生物标志物与BPD发展之间的关系；2)评估有希望的候选基因（GSTP1, SOD3）与BPD风险的遗传相关性，调整重要临床变量，人群混合和多重检测。完成该项目后，Mestan博士将获得生化分析和基因分型技术以及先进的统计和遗传分析方面的基本经验，用于设计和指导BPD的未来研究及其结果。

项目成果

Fetal growth restriction and pulmonary hypertension in premature infants with bronchopulmonary dysplasia.

胎儿生长限制和支气管肺发育不良的早产儿的肺部高血压。

• DOI: 10.1038/jp.2012.164
• 发表时间: 2013-07
• 期刊: JOURNAL OF PERINATOLOGY
• 影响因子: 2.9
• 作者: Check, J.;Gotteiner, N.;Liu, X.;Su, E.;Porta, N.;Steinhorn, R.;Mestan, K. K.
• 通讯作者: Mestan, K. K.

Cord blood biomarkers of vascular endothelial growth (VEGF and sFlt-1) and postnatal growth: a preterm birth cohort study.

血管内皮生长（VEGF 和 sFlt-1）和产后生长的脐带血生物标志物：一项早产队列研究。

• DOI: 10.1016/j.earlhumdev.2014.01.003
• 发表时间: 2014
• 期刊: Early human development
• 影响因子: 2.5
• 作者: Voller,StephannieBaehl;Chock,Susanne;Ernst,LindaM;Su,Emily;Liu,Xin;Farrow,KathrynN;Mestan,KarenK
• 通讯作者: Mestan,KarenK

Maternal obesity, diabetes mellitus and cord blood biomarkers in large-for-gestational age infants.

• DOI: 10.1055/s-0036-1586378
• 发表时间: 2010-01-01
• 期刊: Journal of pediatric biochemistry
• 作者: Mestan K;Ouyang F;Matoba N;Pearson C;Ortiz K;Wang X
• 通讯作者: Wang X