Inflammatory Cytokine Polymorphisms, Air Pollution, and Very Preterm Birth

炎症细胞因子多态性、空气污染和极早产

基本信息

批准号：
8491819
负责人：
Ondine von Ehrenstein
金额：
$ 23.16万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8491819
关键词：
Accounting Address Air Pollutants Air Pollution Behavioral Biological Birth Certificates Caliber California Case-Control Studies Child County Data Data Set Dependence Environmental Risk Factor Epidemiologic Studies Epidemiology Etiology Exposure to Fetus Gene-Modified Genes Genetic Genetic Polymorphism Genotype Gestational Age Goals Health Hospitals Immune response Incidence Infant Infant Mortality Inflammation Inflammatory Inflammatory Response Intervention Knowledge Link Live Birth Location Logistics Lung diseases Maternal Behavior Maternal Exposure Measures Medical Modeling Monitor Mothers Nested Case-Control Study Newborn Infant Nitrogen Dioxide Nitrogen Oxides Outcome Ozone Particulate Matter Pathway interactions Pharmaceutical Preparations Policies Population Pregnancy Premature Birth Premature Labor Prevalence Preventive Recording of previous events Records Reporting Resources Risk Single Nucleotide Polymorphism Statistical Models Study Subject Techniques Time United States Variant Woman air monitoring base case control cytokine gene environment interaction genetic variant high risk land use nervous system disorder novel particle pollutant prenatal public health relevance screening trafficking

项目摘要

DESCRIPTION (provided by applicant): We proposes to examine the hypotheses that maternal exposure to air pollutants during pregnancy is associated with an increased risk of very preterm birth (VPTB, <32 weeks gestation), and that polymorphisms in inflammatory genes modify the influence of air pollution on the risk of VPTB. Relying on an existing, well- conducted case-control study of VPTB and combining it with our expertise and resources in air pollution exposure assessment and in analyzing gene-environment interactions, we propose to conduct the first epidemiologic study of gene-environment interactions and VPTB. VPTB is the most frequent cause of infant mortality in the US, and a main contributor to neurological and pulmonary disorders in children with infants born at lower gestational age at highest risk [1-7]. PTB occurs in ~12% of live births in the US [5], with VPTB at a prevalence of ~2% [9]. Experts agree that the cause of PTB is multifactorial, including genetics, maternal behaviors, and environmental factors [10, 11]. Although growing evidence is linking PTB to ambient air pollution, the biological mechanisms underlying the reported associations are still unknown. Inflammation is one primary pathway believed to be involved in air pollution-induced health effects [19-21]. To date, no study has addressed gene-environmental interaction between air pollution and inflammatory genetic variants in the etiology of PTB. We propose to use data from the CA Very Preterm Birth (CVPTB) Study, a nested case-control study of VPTB from 5 counties in Southern CA known for high particulate matter, ozone, and traffic exposures. Fifty single nucleotide-polymorphisms (SNPs) previously shown to be related to PTB in 26 inflammatory/immune response pathway genes were genotyped in mother-infant pairs to examine their contributions to VPTB. We will utilize a combination of extensive air monitoring data and air pollution modeling approaches (land use regression (LUR), CALINE4, kriging) to estimate air pollution exposures in pregnancy for CVPTB Study subjects. In addition to birth certificates records, we will have available to us data from medical chart reviews for VPTB cases and residential history during mid-pregnancy from prenatal screening records which will strengthen the exposure assessment compared to previous studies relying solely on delivery addresses from birth certificates. We will also have available to us demographic and maternal medication data from prenatal screening records. Thus, the CVPTB dataset, combined with our exceptional expertise and resources in air pollution assessment and in assessing gene-environment interaction, provides a novel and unique opportunity to - for the very first time - explore gene-environment interactions as contributors to the risk of VPTB, specifically the interactions between air pollution and specific SNPs involved in inflammatory pathways. The proposed study will provide invaluable information to better understand the mechanisms linking air pollution to premature birth, especially VPTB, providing scientific data and support for air pollution regulatory policies which consider the developing fetus as a sensitive sub-population that needs greater protection.

描述（由申请人提供）：我们提议研究假设，即怀孕期间的孕产妇暴露于空气污染物与非常早产的风险增加有关（VPTB，妊娠32周），炎症基因中的多态性改变了空气污染对VPTB风险的影响。依靠现有的，经过良好的VPTB的病例对照研究，并将其与我们在空气污染暴露评估中的专业知识和资源相结合，并在分析基因环境相互作用时，我们建议进行基因 - 环境相互作用和VPTB的首次流行病学研究。 VPTB是美国婴儿死亡率最常见的原因，也是胎儿患儿童的神经和肺部疾病的主要促成者，处于最高风险[1-7]。 PTB发生在约12％的现场出生中[5]，VPTB的患病率为约2％[9]。专家认为，PTB的原因是多因素，包括遗传学，孕产妇行为和环境因素[10，11]。尽管越来越多的证据将PTB与环境空气污染联系起来，但所报告关联的生物学机制仍然未知。炎症是据信与空气污染引起的健康作用有关的主要途径[19-21]。迄今为止，尚未解决PTB病因中空气污染与炎症遗传变异之间的基因 - 环境相互作用。我们建议使用CA非常早产（CVPTB）研究中的数据，这是一项嵌套的病例对照研究，对来自南部CA的5个县的VPTB研究以高颗粒物，臭氧和交通曝光而闻名。先前证明的50个单核苷酸 - 多态性（SNP）与26个炎症/免疫反应途径中的PTB相关，在母侵对中是基因分型的，以检查其对VPTB的贡献。我们将利用广泛的空气监测数据和空气污染建模方法（土地利用回归（LUR），Caline4，Kriging）的组合来估计CVPTB研究对象怀孕期间的空气污染暴露。除了出生证书记录外，我们还将通过医学图表审查VPTB病例的医学图表和居住历史记录，从产前筛查记录中获得居住记录，与以前的研究相比，这将加强暴露评估，仅依赖于出生证明的交付地址。我们还将从产前筛查记录中为美国的人口统计和孕产妇药物数据提供。因此，CVPTB数据集与我们在空气污染评估中的非凡专业知识和资源相结合，在评估基因环境的互动中，为第一次探索了基因环境相互作用提供了一个新颖而独特的机会，作为对VPTB的风险的贡献者，尤其是空气污染与伴有特定的SNPS相互作用的相互作用。拟议的研究将提供宝贵的信息，以更好地了解将空气污染与早产相关的机制，尤其是VPTB，提供科学数据并为空气污染调节政策提供支持，这些政策将发展中的胎儿视为需要更大保护的敏感亚人群。