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.

非西班牙裔黑人妇女的早产可能性高1.5倍（PTB； <37周妊娠） 与非西班牙裔白人妇女相比（14％比9％）。早产是新生儿的主要原因 黑人婴儿的发病率。怀孕的黑人妇女也更有可能体验种族歧视 和抑郁症状，维生素D缺乏症的风险更高[等离子体25（OH）D浓度<20 与白人妇女相比，ng/ml]。种族歧视，抑郁症状和维生素D缺乏症 与促炎性细胞因子的增加有关（例如TNF-α，IL-6），但研究尚未 检查了与PTB的这些因素的潜在途径，研究了免疫相关基因的基因表达。 周围单核细胞（PBMC）含有淋巴细胞，单核细胞和树突状细胞，所有这些都是 对于免疫功能很重要，可以表达促炎和抗炎细胞因子。通过检查 在黑人孕妇队列中，PBMC的基因表达模式，它可以阐明不同或 重叠的途径（例如种族歧视，抑郁症状）和 维生素D状态增加了PTB的风险。 使用来自参加Giurgescu博士（Mentor）R01研究的168位怀孕黑人妇女的数据，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，全身性 出生时炎症和妊娠年龄（GA）。妇女完成了问卷调查，并在8-- 妊娠18周。问卷数据，血浆细胞因子（TNF-α，IL-6，IL-8，IL-4，IL-4，IL-10，INF-γ）和GA 出生时将从父母的研究中获得。冷冻血浆和PBMC样品存储在Mentor's 实验室。血浆25（OH）D浓度将通过液相色谱/ 质谱法。 VDBP基因型将通过Taqman分析评估使用核中提取的DNA 从PBMC中分离出来。在Kraus博士（Co-Incertor）的监督下，我将进行批量RNA测序 （RNA-seq）在冷冻PBMC上。我的目标是：（目标1）探索免疫细胞基因的差异基因表达 在（1）患有PTB的妇女和有期出生的妇女之间； （2）维生素D缺乏症和女性的女性 维生素D受苦； （目标2）检查种族歧视，抑郁症的途径 症状，血浆25（OH）D，VDBP基因型，表达不同的基因（在AIM 1中鉴定），并且 出生时与GA有关的系统性炎症。拟议的，严格的培训计划和经验丰富的 Menorship Team将加速我通往独立调查员的道路，让我有时间学习尖端 使用基因组学和转录组学，OMICS分析和生物信息学的发展能力的研究 数据，并获得团队领导能力。这项研究的结果将为NIH提供初步数据 R01研究以识别PTB的预测生物标志物。