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

• 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
• 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

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)：我们建议检验以下假设，即孕妇在怀孕期间暴露于空气污染物与早产风险的增加有关(妊娠32周)，以及炎症基因的多态改变了空气污染对VPTB风险的影响。在现有的一项进行良好的VPTB病例对照研究的基础上，结合我们在空气污染暴露评估和分析基因-环境相互作用方面的专业知识和资源，我们建议进行第一次关于基因-环境相互作用和VPTB的流行病学研究。VPTB是美国最常见的婴儿死亡原因，也是导致低胎龄婴儿风险最高的儿童神经和肺部疾病的主要因素[1-7]。在美国，活产儿中约12%会发生肺结核[5]，而肺结核病的患病率约为2%[9]。专家们一致认为，肺结核的原因是多因素的，包括遗传、母亲行为和环境因素[10，11]。尽管越来越多的证据将肺结核与环境空气污染联系起来，但已报道的这种联系背后的生物学机制仍不清楚。炎症是空气污染引起的健康影响的主要途径之一[19-21]。到目前为止，还没有关于空气污染和炎性遗传变异在肺结核病因学中的基因-环境相互作用的研究。我们建议使用来自CA非常早产(CVPTB)研究的数据，这是一项嵌套的VPTB病例对照研究，来自加利福尼亚州南部以高颗粒物、臭氧和交通暴露而闻名的5个县。在26个炎症/免疫反应途径基因中发现了50个与肺结核相关的单核苷酸多态(SNPs)，并在母婴配对中进行了基因分型，以探讨它们对VPTB的作用。我们将结合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、克里格法)来评估CVPTB研究对象孕期的空气污染暴露。除了出生证明记录外，我们还将从产前筛查记录中获得VPTB病例的病历审查和中期住院史的数据，这将与以前仅依赖出生证明中的分娩地址的研究相比，加强暴露评估。我们还将获得产前筛查记录中的人口统计和产妇用药数据。因此，CVPTB数据集与我们在空气污染评估和评估基因-环境相互作用方面的卓越专业知识和资源相结合，提供了一个新颖和独特的机会，首次探索作为VPTB风险贡献者的基因-环境相互作用，特别是空气污染和参与炎症途径的特定SNP之间的相互作用。这项拟议的研究将提供宝贵的信息，以更好地了解空气污染与早产，特别是VPTB之间的联系机制，为空气污染监管政策提供科学数据和支持，这些政策将发育中的胎儿视为需要更多保护的敏感亚群。