Epigenetic and Biobehavioral Determinants of Preterm Birth in Black Women

黑人女性早产的表观遗传和生物行为决定因素

• 批准号: 8775415
• 负责人: ANNE Lang DUNLOP
• 金额: $ 39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-10 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8775415
• 关键词: 25-hydroxyvitamin D; Accounting; Address; Affect; African American; Appointment; Area; Award; Behavioral; Biological; Biological Markers; Biology; Birth; Body mass index; Caucasians; Caucasoid Race; Chronic stress; Clinical Sciences; Cross-Sectional Studies; DNA Methylation; Data; Development; Enrollment; Epidemiology; Epigenetic Process; Ethnic Origin; Folate; Functional disorder; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Glucocorticoids; Goals; Home environment; Hospitals; Human Resources; Hydrocortisone; Individual; Infant Mortality; Inflammation; Inflammatory; Informatics; Institute of Medicine (U.S.); Institutes; Interdisciplinary Study; Investigation; Link; Literature; Longitudinal Studies; Maternal and Child Health; Measures; Mediating; Methylation; Micronutrients; Nested Case-Control Study; Nutritional; Nutritional status; Outcome; Participant; Pathway interactions; Pattern; Peripheral; Peripheral Blood Mononuclear Cell; Physiological; Platelet Factor 4; Polyunsaturated Fatty Acids; Population; Pregnancy; Premature Birth; Prenatal care; Psychosocial Stress; Race; Reporting; Reproductive Tract Infections; Research; Research Design; Resistance; Risk; Risk Factors; Scientist; Serum; Socioeconomic Status; Stress; Term Birth; Testing; Third Pregnancy Trimester; Time; Translational Research; United States; United States National Institutes of Health; Universities; Variant; Woman; biobehavior; biopsychosocial; case control; cohort; cytokine; experience; genome-wide; health disparity; infant morbidity/mortality; insight; minority health; nutrition; pregnant; psychosocial; public health relevance; socioeconomics; success; theories

DESCRIPTION (provided by applicant): Preterm birth (PTB, birth prior to 37 weeks' gestation) is a leading cause of infant mortality. Of the known risk factors for PTB, among the strongest is African American (AA) race. Compared to Caucasians, AA women have more than 1.5 times the risk of PTB (16.8% vs. 10.5%). The proposed research will investigate whether specific bio behavioral factors linked to PTB influence the epigenetic regulation of genes to promote PTB in AA women. This research will contribute to a bio psychosocial understanding of within-race risk for PTB, providing insight into important risk and protective factors relevant to AA women. The proposed research is consistent with frameworks for eliminating racial disparities, which recognize the need to study risks within-race as a vital first step, and is congruent with the National Institute of Minority Health and Health Disparities goal of promoting understanding of the biological mechanisms involved in conditions that disproportionately affect health disparity populations. To evaluate the hypothesis that epigenetic mechanisms mediate the relationship between specific bio behavioral factors and PTB for AA women, the proposed study will leverage bio behavioral and biologic data from an on-going longitudinal study of preterm birth in AA women (R01 NR014800) that is enrolling a socioeconomically diverse cohort of H 960 pregnant AA women and collecting data during prenatal care appointments (at 10-14 and 26-30 weeks' gestation) and at delivery. Using a nested case-control approach, cases are designated as those who experience PTB (an estimated 125 cases) and controls as those who experience a term birth. Building from this study design, we will: (1) characterize PBMC DNA methylation and RNA expression patterns over the course of pregnancy among AA women who deliver preterm and at term; (2) identify bio behavioral factors - including nutritional status, stress, an reproductive tract infections - that influence patterns of peripheral DNA methylation and RNA expression; (3) evaluate associations between PTB and both DNA methylation and RNA expression among AA women that are independent of the bio behavioral factors and (4) determine whether these epigenetic differences can be detected in the second and/or third trimester. The success of this research is supported by a multidisciplinary collaboration of clinicians, basic and translational scientists representing expertise in obstetrical outcomes and maternal-child health, genetics and epigenetics, nutrition, stress, epidemiology and informatics; the overlap of key personnel for the proposed study and the on-going R01 'Bio behavioral Determinants of the Micro biome and Preterm Birth for Black Women'; and support from Emory University's Clinical and Translational Science Institute (CTSA award # NIH UL1TR000454). Finally, Atlanta is home to AA women of broad socioeconomic status who are served by Emory's affiliated delivery hospitals, allowing for sufficient variation in the bio behavioral factrs under study to distinguish independent and interactive effects on DNA methylation and, ultimately, on the risk of PTB.

描述（由申请人提供）： 早产（PTB，妊娠 37 周之前出生）是婴儿死亡的主要原因。在已知的 PTB 风险因素中，最严重的是非裔美国人 (AA) 种族。与白种人相比，AA 女性患 PTB 的风险是白人的 1.5 倍以上（16.8% vs. 10.5%）。拟议的研究将调查与 PTB 相关的特定生物行为因素是否影响基因的表观遗传调控，从而促进 AA 女性的 PTB。这项研究将有助于对 PTB 种族内风险的生物心理社会理解，深入了解与 AA 女性相关的重要风险和保护因素。拟议的研究符合消除种族差异的框架，该框架认识到研究种族内风险的必要性是至关重要的第一步，并且与国家少数民族健康和健康差异研究所的目标一致，即促进对不成比例地影响健康差异人群的条件所涉及的生物机制的理解。 为了评估表观遗传机制介导 AA 女性特定生物行为因素与 PTB 之间关系的假设，拟议的研究将利用正在进行的 AA 女性早产纵向研究 (R01 NR014800) 的生物行为和生物学数据，该研究招募了社会经济多样化的 H 960 AA 孕妇队列，并在产前护理预约期间收集数据 （妊娠 10-14 周和 26-30 周时）和分娩时。使用巢式病例对照方法，病例被指定为经历过 PTB 的患者（估计有 125 例），对照被指定为经历足月分娩的患者。根据这项研究设计，我们将：(1) 描述早产和足月的 AA 女性在怀孕过程中 PBMC DNA 甲基化和 RNA 表达模式的特征； (2) 确定影响外周 DNA 甲基化和 RNA 表达模式的生物行为因素，包括营养状况、压力、生殖道感染； (3) 评估 AA 女性中 PTB 与 DNA 甲基化和 RNA 表达之间的关联，这些关联与生物行为因素无关，并且 (4) 确定这些表观遗传差异是否可以在妊娠中期和/或晚期检测到。这项研究的成功得到了临床医生、基础科学家和转化科学家的多学科合作的支持，这些科学家代表了产科结果和母婴健康、遗传学和表观遗传学、营养、压力、流行病学和信息学方面的专业知识；拟议研究的关键人员与正在进行的 R01“微生物群落的生物行为决定因素和黑人妇女早产”的重叠；以及埃默里大学临床和转化科学研究所的支持（CTSA 奖# NIH UL1TR000454）。最后，亚特兰大是具有广泛社会经济地位的 AA 妇女的家园，她们由埃默里大学附属分娩医院提供服务，允许所研究的生物行为因素存在足够的变化，以区分对 DNA 甲基化的独立影响和交互影响，并最终区分对 PTB 风险的影响。