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）是婴儿死亡率的主要原因。 PTB的已知危险因素之一是非裔美国人（AA）种族。与高加索人相比，AA妇女的风险是PTB的1.5倍以上（16.8％比10.5％）。拟议的研究将研究与PTB相关的特定生物行为因素是否影响基因的表观遗传调节，以促进AA妇女的PTB。这项研究将有助于对PTB赛场内风险的生物心理社会理解，从而洞悉与AA妇女有关的重要风险和保护因素。拟议的研究与消除种族差异的框架是一致的，这些框架认识到需要在赛场内研究风险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是一致的，旨在促进对疾病中涉及的生物学机制的理解，从而对健康差异不成比例。 为了评估以下假说，即表观遗传机制介导了AA妇女的特定生物行为因素与PTB之间的关系，拟议的研究将利用正在进行的AA妇女早产的纵向研究中的生物行为和生物学数据（R01 NR014800）（R01 NR014800）（R01 NR014800）在社会经济学期间培养了H 960 AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA AA 960 AA AA AA AA AA AA AA AA AA AA AA AA。 （妊娠10-14和26-30周）和交货时。使用嵌套的病例对照方法，案件被指定为经历PTB（估计125例）并控制为年定期出生的案例。通过这项研究设计，我们将：（1）在AA妇女中妊娠过程中PBMC DNA甲基化和RNA表达模式的特征； （2）确定影响周围DNA甲基化和RNA表达的模式的生物行为因素 - 包括营养状况，压力，生殖道感染 - （3）评估独立于生物行为因素的AA女性中PTB与DNA甲基化和RNA表达之间的关联，（4）确定是否可以在第二和/或三个月中检测到这些表观遗传差异。这项研究的成功得到了临床医生，基础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以及母婴健康，遗传学和表观遗传学，营养，压力，流行病学和信息学的专业知识；拟议研究的关键人员的重叠以及黑人妇女的微生物群体和早产的持续R01'生物行为决定因素''；以及埃默里大学临床和转化科学研究所（CTSA奖＃NIH UL1TR000454）的支持。最后，亚特兰大是具有广泛社会经济地位的AA妇女的所在地，这些妇女由埃默里（Emory）附属的送货医院服务，从而使正在研究的生物行为factrs有足够的差异，以区分对DNA甲基化的独立和交互作用，并最终对PTB的风险区分。