Genomic signatures of inflammation: Pathways of racial discrimination, depressive symptoms, Vitamin D status with preterm birth among Black women

非西班牙裔黑人妇女早产的可能性是非西班牙裔黑人妇女早产的1.5倍（PTB; < 37周妊娠） 与非西班牙裔白色女性相比（14%对9%）。早产是新生儿死亡的主要原因。 黑人婴儿的发病率。怀孕的黑人妇女也更容易受到种族歧视 和抑郁症状，并有较高的风险，维生素D缺乏[血浆25（OH）D浓度<20 ng/ml]与白色女性相比。种族歧视、抑郁症状和维生素D缺乏症 与增加的促炎细胞因子（例如，TNF-α，IL-6），但研究没有 检测了免疫相关基因的基因表达，作为这些因素与PTB的潜在途径。 外周单核细胞（PBMC）含有淋巴细胞、单核细胞和树突状细胞，所有这些都是 对免疫功能很重要，并能表达促炎和抗炎细胞因子。通过检查 基因表达模式的PBMC在一个队列的黑人孕妇，它可以阐明不同的或 社会心理因素（如种族歧视、抑郁症状）和 维生素D状况会增加患肺结核的风险。 使用来自168名黑人孕妇的数据，他们参加了Giovescu博士（导师）的R 01研究，我将 研究种族歧视、抑郁症状、维生素D结合蛋白 （VDBP）基因型，血浆25（OH）D浓度，免疫细胞基因的基因表达，系统性 炎症和出生时胎龄（GA）。妇女们完成了问卷调查，并在8- 怀孕18周。问卷调查数据、血浆细胞因子（TNF-α、IL-6、IL-8、IL-4、IL-10、INF-γ）水平和GA 将从母研究中获得。冷冻血浆和PBMC样本储存在Mentor的 实验室将使用液相色谱法测量冷冻样本的血浆25（OH）D浓度。 质谱分析法来将使用从细胞核中提取的DNA通过TaqMan分析评估VDBP基因型 分离自PBMC。在Kraus博士（共同导师）的监督下，我将进行批量RNA测序 （RNA-seq）。本研究的目的是：（1）探索免疫细胞基因的差异表达 （1）PTB妇女和足月分娩妇女;（2）维生素D缺乏妇女和 维生素D充足;（目的2）检查种族歧视，抑郁症， 症状、血浆25（OH）D、VDBP基因型、差异表达基因（在目标1中鉴定），以及 出生时与GA相关全身性炎症。建议，严格的培训计划和丰富的经验， 导师团队将加速我的独立调查员之路，让我有时间学习前沿知识， 使用基因组学和转录组学进行研究，培养组学分析和生物信息学的能力 数据，并获得团队领导技能。这项研究的结果将为NIH提供初步数据。 R 01研究旨在确定PTB的预测性生物标志物。

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.