Pathways linking social disparities, inflammation, and health across generations

描述(由申请人提供)：社会经济地位(SES)的维度被人口统计学和行为学家认为是疾病的“根本原因”，这些疾病通过更接近的途径影响个人健康，以及人口健康方面的差异。炎症是正常免疫功能的重要组成部分，但妊娠期过度或失调的炎症会导致不良的出生结果，可能会为下一代建立不良的健康轨迹。社会经济因素是炎症变化的重要决定因素，但SES在整个生命过程中的影响途径尚不清楚。该项目的具体目标是：1)验证非临床环境中测量炎症的微创方法；2)调查早期生活环境(妊娠、婴儿)如何影响成年后妊娠期间的炎症；3)分析孕期炎症作为出生结果的预测因子；以及4)评估炎症基因的表观遗传修饰，以此作为解释早期生活环境长期影响的机制。该项目专注于干血斑(DBS)--从简单的手指棒上收集的全血液滴--作为静脉穿刺术的微创替代方案，便于以最低的成本或负担从大量人身上采集血液。测量促炎和抗炎活性的方法(细胞因子水平，基因表达模式)将被应用于一项大型的、正在进行的出生队列研究，该研究具有30年的前瞻性收集数据。DBS样本将在怀孕7个月期间从孕妇身上收集，并对炎症模式进行测量，以检验这一假设，即生命早期的社会经济状况是成年后怀孕期间炎症调节的重要预测因素。婴儿期的营养、传染病和心理社会环境也将被调查，作为调节早期生活SES对成年炎症影响的中间途径。孕妇将在分娩时进行跟踪，以调查怀孕期间的炎症是否与早产或较低的后代出生体重有关。将对样本进行炎症基因启动子区域的甲基化测量，以调查表观遗传过程是否作为一种机制，通过这种机制在怀孕期间“记住”早期生活环境，并塑造下一代的健康。新的微创方法的发展将促进未来以社区为基础的炎症研究。这项研究的结果将促进对炎症的科学理解，因为炎症是社会环境导致不良生育结果和一生中健康差异的关键途径，可能会在几代人之间造成这种差异。

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.