Graduation Year

2022

Document Type

Thesis

Degree

M.S.P.H.

Degree Name

MS in Public Health (M.S.P.H.)

Degree Granting Department

Public Health

Major Professor

Derek Wildman, Ph.D.

Committee Member

Monica Uddin, Ph.D.

Committee Member

Jamie Corvin, Ph.D.

Committee Member

Chengqi Wang, Ph.D.

Keywords

preterm birth, gene expression, epigenetic, hypothalamic-pituitary-adrenal axis

Abstract

Preterm birth is the event of spontaneous birth prior to 37 weeks of gestation. In the United States, 1 in 10 babies are born prematurely. Low gestational age has been linked with increased morbidity and mortality. Preterm birth is multifactorial, where a myriad of contributors have been identified to include inflammation, chorioamnionitis, and inflammatory conditions to include hypertension and diabetes. To further explore the role inflammation plays in low gestational age, a literature review was done using PubMed. Two classes of inflammation quickly emerged: Pathogen born intra-amniotic inflammation and Sterile intra-amniotic inflammation. The latter form of inflammation has no identifiable source. Hypothalamic- pituitary-adrenal axis [HPA-axis] dysregulation was explored as a possible source to sterile intra- amniotic inflammation. Data was obtained from an epigenetic wide association study that analyzed 157 peripheral blood samples from infants using a 450k array to output β-values. Two gene lists were created, the glucocorticoid receptor regulatory network that details 82 genes that are pertinent to HPA-axis function and a “regulation of cytokine production involved in inflammatory response” gene list was obtained from Gene Ontology. Gene tables were created to identify CpG sites from the 450k array that are associated with the genes of interest. A Wilcoxon sum rank test was used to evaluate differential methylation between infants who did and did not experience chorioamnionitis with p-adjusted values < 0.1 were considered significant. Nine genes had CpG sites with differential methylation including FKBP5, EP300, GATA3, GSK3B, IL6R, NFATC1, NR3C1, SAMARCA4, HIF1AN.

Included in

Genetics Commons

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