Pathways linking social disparities, inflammation, and health across generations

连接代际社会差异、炎症和健康的途径

• 批准号: 8576859
• 负责人: THOMAS W MC DADE
• 金额: $ 31.56万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-18 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8576859
• 关键词: Accounting; Adult; Anti-Inflammatory Agents; Anti-inflammatory; Behavioral; Biological; Birth; Birth Weight; Blood; Blood specimen; Cardiovascular Diseases; Child; Chronic; Clinic; Cohort Studies; Collection; Communicable Diseases; Communities; Data; Degenerative Disorder; Development; Diabetes Mellitus; Dimensions; Discipline; Disease; Drops; Economic Factors; Environment; Environmental Impact; Environmental Risk Factor; Epigenetic Process; Equation; Fingers; Foundations; Functional disorder; Future; Gene Expression; Gene Expression Profile; Generations; Genes; Health; Individual; Individual Differences; Inflammation; Inflammatory; Laboratories; Life; Life Cycle Stages; Life Experience; Link; Long-Term Effects; Low Birth Weight Infant; Measures; Mediating; Mediator of activation protein; Methods; Methylation; Modeling; Modification; Molecular; Mothers; Nutritional; Outcome; Pathway interactions; Pattern; Personal Satisfaction; Philippines; Physiological; Positioning Attribute; Prediabetes syndrome; Pregnancy; Pregnant Women; Premature Birth; Process; Promoter Regions; Protocols documentation; Public Health; Regulation; Research; Resolution; Risk; Sampling; Scientific Advances and Accomplishments; Scientist; Series; Shapes; Signal Pathway; Social Environment; Socioeconomic Status; Spottings; Testing; Variant; Venipunctures; Whole Blood; base; cost; cytokine; disorder risk; early experience; experience; follow-up; forging; immune function; infancy; intergenerational; minimally invasive; next generation; offspring; population health; prevent; psychosocial; public health relevance; social; social disparities; socioeconomics; transmission process

DESCRIPTION (provided by applicant): Dimensions of socioeconomic status (SES) are recognized by demographic and behavioral scientists as "fundamental causes" of disease that operate through more proximate pathways to shape individual health, as well as disparities in population health. Inflammation is an important part of normal immune function, but excessive or dysregulated inflammation during gestation contributes to adverse birth outcomes, potentially setting up poor trajectories of health for the next generation. Socio-economic factors are important determinants of variation in inflammation, but the pathways of SES influence across the life course are not known. The specific aims of this project are: 1) To validate minimally-invasive methods for measuring inflammation in non-clinical settings; 2) To investigate how environments in early life (gestation, infancy) influence inflammation in adulthood, during pregnancy; 3) To analyze inflammation during pregnancy as a predictor of birth outcomes; and 4) To evaluate epigenetic modifications to inflammatory genes as a mechanism accounting for long-term effects of early life environments. The project focuses on dried blood spots (DBS) - drops of whole blood collected from a simple finger stick - as a minimally-invasive alternative to venipuncture that facilitates the collection of blood from large numbers of people, at minimal cost or burden. Methods for measuring pro- and anti-inflammatory activity (cytokine levels, patterns of gene expression) will be applied to a large, ongoing birth cohort study with 30 years of prospectively collected data. DBS samples will be collected from pregnant women during the 7th gestational month, and patterns of inflammation measured to test the hypothesis that socioeconomic status early in life is a significant predictor of the regulation of inflammation in adulthood, during pregnancy. Nutritional, infectious disease and psychosocial environments in infancy will also be investigated as intermediate pathways mediating the influence of early life SES on inflammation in adulthood. Pregnant women will be followed up at delivery, to investigate whether inflammation during pregnancy is associated with pre-term delivery or lower offspring birth weight. Samples will be measured for methylation of promoter regions of inflammatory genes to investigate whether epigenetic processes serve as a mechanism through which early life environments are "remembered" during pregnancy and shape the health of the next generation. The development of new, minimally-invasive methods will facilitate future community-based research on inflammation. Findings from the study will advance scientific understanding of inflammation as a key pathway through which social environments contribute to adverse birth outcomes and disparities in health over the life course, and potentially across generations.

描述（由申请人提供）：社会经济地位（SES）的维度被人口和行为科学家认为是疾病的“根本原因”，通过更接近的途径来塑造个人健康，以及人口健康的差异。炎症是正常免疫功能的重要组成部分，但妊娠期间过度或失调的炎症会导致不良的出生结果，可能会为下一代带来不良的健康轨迹。社会经济因素是炎症变化的重要决定因素，但SES影响整个生命过程的途径尚不清楚。该项目的具体目标是：1）验证用于测量非临床环境中炎症的微创方法; 2）调查早期生活环境如何影响炎症。（妊娠期、婴儿期）影响成年期、妊娠期间的炎症; 3）分析妊娠期间的炎症作为出生结果的预测因子;和4）评估炎症基因的表观遗传修饰作为解释早期生活环境的长期影响的机制。该项目的重点是干血点（DBS）-从简单的手指针刺中收集的全血滴-作为静脉穿刺的微创替代方案，便于以最小的成本或负担从大量人群中收集血液。测量促炎和抗炎活性（细胞因子水平、基因表达模式）的方法将应用于一项大型、正在进行的出生队列研究，该研究前瞻性收集了30年的数据。DBS样本将从妊娠第7个月的孕妇中收集，并测量炎症模式，以检验生命早期的社会经济地位是妊娠期间成年炎症调节的重要预测因素的假设。婴儿期的营养、传染病和心理社会环境也将作为中介途径来研究，这些中介途径介导了早期生活SES对成年期炎症的影响。孕妇将在分娩时接受随访，以调查妊娠期间的炎症是否与早产或后代出生体重较低有关。将测量样本的炎症基因启动子区域的甲基化，以研究表观遗传过程是否作为一种机制，通过这种机制，早期生活环境在怀孕期间被“记住”，并塑造下一代的健康。新的微创方法的开发将促进未来基于社区的炎症研究。这项研究的结果将促进对炎症的科学理解，炎症是社会环境导致不良出生结果和生命过程中健康差异的关键途径，并可能跨代。