Inflammatory Cytokine Polymorphisms, Air Pollution, and Very Preterm Birth
Principal Investigator: Ondine von Ehrenstein
Abstract: 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 , with VPTB at a prevalence of ~2% . 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.
Funding Period: 2013-07-01 - 2015-06-30
more information: NIH RePORT
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