Non-Hispanic Black women are 1.5 times more likely to have preterm birth (PTB; < 37 weeks gestation)
compared with non-Hispanic White women (14% vs 9%). Preterm birth is the leading cause of neonatal
morbidity among Black infants. Pregnant Black women are also more likely to experience racial discrimination
and depressive symptoms and have higher risk for vitamin D deficiency [plasma 25(OH)D concentration <20
ng/ml] compared with White women. Racial discrimination, depressive symptoms and vitamin D deficiency
have been associated with increased pro-inflammatory cytokines (e.g.,TNF-α, IL-6), but research has not
examined the gene expression of immune-related genes as potential pathways of these factors with PTB.
Peripheral mononuclear cells (PBMCs) contain lymphocytes, monocytes and dendritic cells all of which are
important for immune function and can express both pro- and anti-inflammatory cytokines. By examining the
gene expression pattern of PBMCs in a cohort of Black pregnant women, it could elucidate distinct or
overlapping pathways by which psychosocial factors (e.g. racial discrimination, depressive symptoms) and
vitamin D status increase risk for PTB.
Using data from 168 pregnant Black women participating in Dr. Giurgescu's (mentor) R01 study, I will
examine the associations among racial discrimination, depressive symptoms, Vitamin D Binding Protein
(VDBP) genotype, plasma 25(OH)D concentration, gene expression of immune cell genes, systemic
inflammation, and gestational age (GA) at birth. Women completed questionnaires and had blood drawn at 8-
18 weeks gestation. Questionnaire data, plasma cytokine (TNF-α, IL-6, IL-8, IL-4, IL-10, INF-γ) levels, and GA
at birth will be available from the parent study. Frozen plasma and PBMC samples are stored in mentor's
laboratory. Plasma 25(OH)D concentration will be measured from frozen samples using liquid chromatography/
mass spectrometry. VDBP genotype will be assessed by TaqMan assays using DNA extracted from nuclei
isolated from PBMCs. Under the supervision of Dr. Kraus (co-mentor), I will conduct bulk RNA sequencing
(RNA-seq) on frozen PBMCs. I aim to: (Aim 1) Explore differential gene expression of immune cell genes
between (1) women with PTB and women with term birth; and (2) women with vitamin D deficiency and women
with vitamin D sufficiency; and (Aim 2) Examine the pathways by which racial discrimination, depressive
symptoms, plasma 25(OH)D, VDBP genotype, differentially expressed genes (identified in Aim 1), and
systemic inflammation relate to GA at birth. The proposed, rigorous training plan and highly experienced
mentorship team will accelerate my path to independent investigator, allowing me time to learn cutting-edge
research using genomics and transcriptomics, develop competency in analysis and bioinformatics of omics
data, and gain team leadership skills. The results from this study will provide the preliminary data for a NIH
R01 study to identify predictive biomarkers for PTB.
