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

炎症的基因组特征：黑人女性种族歧视、抑郁症状、维生素 D 状况与早产的途径

• 批准号: 10449777
• 负责人: Jennifer Woo
• 金额: $ 13.09万
• 依托单位: TEXAS WOMAN'S UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-14 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10449777
• 关键词: 37 weeks gestation; Alleles; Anti-Inflammatory Agents; Bioinformatics; Biological; Biological Assay; Birth; Black American; Black Populations; Black race; Blood; Cell Nucleus; Cells; Competence; DNA; Data; Dendritic Cells; Dihydroxycholecalciferols; Early identification; Enrollment; Foundations; Freezing; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Genomics; Genotype; Gestational Age; Goals; IL8 gene; Immune; Immune system; Immunomodulators; Individual; Infant; Inflammation; Inflammatory; Interferons; Interleukin-1 beta; Interleukin-10; Interleukin-4; Interleukin-6; K-Series Research Career Programs; Laboratories; Lead; Leadership; Learning; Link; Lymphocyte; Maternal-Fetal Exchange; Measures; Mediating; Mentors; Mentorship; Mononuclear; Not Hispanic or Latino; Outcome; Parents; Participant; Pathway interactions; Peripheral; Peripheral Blood Mononuclear Cell; Plasma; Postpartum Depression; Postpartum Women; Pregnancy; Pregnant Women; Premature Birth; Psychosocial Factor; Questionnaires; RNA; Research; Research Personnel; Risk; Role; Sampling; Solid; Supervision; TNF gene; Term Birth; Time; Tissue-Specific Gene Expression; Training; Training Support; Transcription Factor AP-1; Transcriptional Activation; United States National Institutes of Health; Variant; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamin D3 Receptor; Woman; black women; cohort; cytokine; depressive symptoms; differential expression; effective intervention; experience; genome-wide; genomic signature; high risk; immune function; immunoregulation; improved; inflammatory marker; insight; liquid chromatography mass spectrometry; monocyte; neonatal morbidity; predictive marker; pregnant; racial discrimination; skills; systemic inflammatory response; therapy development; transcription factor; transcriptome sequencing; transcriptomics

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.

非西班牙裔黑人女性早产的可能性高出 1.5 倍（PTB；妊娠 < 37 周） 与非西班牙裔白人女性相比（14% vs 9%），早产是新生儿的主要原因。 黑人婴儿的发病率也更容易遭受种族歧视。 和抑郁症状，维生素 D 缺乏的风险较高 [血浆 25(OH)D 浓度 <20 ng/ml] 与白人女性相比。 种族歧视、抑郁症状和维生素 D 缺乏。 与促炎细胞因子（例如 TNF-α、IL-6）增加有关，但研究并未发现 检查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) 包含淋巴细胞、单核细胞和树突状细胞 对免疫功能很重要，并且可以表达促炎和抗炎细胞因子。 一组黑人孕妇中 PBMC 的基因表达模式，它可以阐明不同的或 心理社会因素（例如种族歧视、抑郁症状）和 维生素 D 状态会增加患 PTB 的风险。 使用参与 Giurgescu 博士（导师）R01 研究的 168 名黑人孕妇的数据，我将 检查种族歧视、抑郁症状、维生素 D 结合蛋白之间的关联 (VDBP) 基因型、血浆 25(OH)D 浓度、免疫细胞基因的基因表达、全身 女性在出生时完成问卷调查并抽血。 妊娠 18 周问卷数据、血浆细胞因子（TNF-α、IL-6、IL-8、IL-4、IL-10、INF-γ）水平和 GA。 出生时可从父母研究中获得冷冻血浆和 PBMC 样本，储存在导师的手中。 实验室将使用液相色谱法测量冷冻样品中的血浆 25(OH)D 浓度。 VDBP 基因型将通过 TaqMan 检测使用从细胞核中提取的 DNA 进行评估。 在 Kraus 博士（共同导师）的监督下，我将进行批量 RNA 测序。 （RNA-seq）对冷冻 PBMC 进行分析，我的目标是：（目标 1）探索免疫细胞基因的差异基因表达。 (1) 患有 PTB 的女性和足月分娩的女性；以及 (2) 缺乏维生素 D 的女性和女性； 维生素 D 充足；以及（目标 2）研究种族歧视、抑郁症的传播途径 症状、血浆 25(OH)D、VDBP 基因型、差异表达基因（目标 1 中确定），以及 全身炎症与出生时的GA有关。建议的、严格的训练计划和丰富的经验。 导师团队将加速我成为独立调查员的道路，让我有时间学习前沿技术 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。 R01 研究旨在确定 PTB 的预测生物标志物。