Date of Award

January 2014

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Nursing

First Advisor

Denise M. Korniewicz

Abstract

Group B streptococcus (GBS) is the leading cause of infectious neonatal morbidity and mortality in the United States. Maternal GBS colonization is the primary risk factor associated with neonatal infection. However, maternal risk factors for GBS colonization are ambiguous. A conceptual framework of gene-environment interactions guided the approach for this study analyzing DNA methylation, serum cytokines, and vitamin D levels. The purpose of this study was to identify potential maternal biomarkers associated with GBS colonization. Descriptive statistics were conducted to depict sample characteristics (n=42 pregnant women) and identify potential confounding variables including, but not limited to: medical history, race, weight, and infections. A series of repeated measures ANOVAs were performed to compare each of three serum cytokines (TNF-alpha, IL-6 and IL-10) and vitamin D levels between the two groups in each trimester of pregnancy. All statistical analyses were completed using a two-tailed alpha of < 0.05 or 95% confidence interval. Mean differences of greater than 20% in DNA methylation of maternal white blood cells collected in the first trimester were analyzed using a false discovery rate of 0.05 to determine significance, as well as independent sample t-tests with a p-value of 0.05 using the Illumina Infinium platform and grouped by GBS status (n=9/group) identified in the third trimester. Function of differentially methylated genes was determined using DAVID Bioinformatics software to identify clinically relevant findings. No statistically significant differences in IL-6 F(2, 80) = 2.99, p = 0.056; IL-10 F(2, 80) = 0.445, p = 0.642; TNF-alpha F(2, 80) = 2.187, p = 0.119; or vitamin D F(1.380, 55.218) = 0.882, p = 0.384 were identified between GBS positive and negative women during pregnancy. Analysis of DNA methylation indicates there are no statistically significant differences between GBS positive and GBS negative women using and FDR of 0.05. When a less stringent p-value of 0.05 was applied, 125 CpG sites differed by 20% or more between GBS positive versus negative women and different results are yielded using multiple statistical approaches (GenomeStudio versus R). Functional analysis suggests genes with methylation differences in the cell morphogenesis cluster may be associated with GBS colonization, although the significance is questionable.

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