Epidemiology, Biomarkers and Exposure Assessment of Metals

项目4：摘要 项目4是一个生物医学项目，是达特茅斯超级基金研究计划的组成部分。 在过去的18年里，我们设计并测试了衡量环境相关水平的方法 接触金属和应用新的生物标志物，暴露，敏感性和早期反应 美国大规模、以人群为基础的流行病学研究。到目前为止，我们已经测试了超过8000个家庭 砷(As)，其中3,500多个有私人供水系统。数据的地理信息系统分析(在中执行 与痕量元素分析核心的合作)显示了明显的高家庭用水集群 级别。在过去的五年里，我们成功地建立了一个怀孕队列，这些女性使用私人 这些聚集区之一的油井。到目前为止，在检测的家庭自来水样本中，约15%超过了 美国环保局规定的最高污染物水平为10？g/L。在未来五年，我们将 在与规划和现有的Superfund站点相邻的另一个集群区域开始招聘。而当 有证据表明，AS与成人发病的糖尿病和高血压有关，它对这些结果的影响 在怀孕期间是不确定的。因此，我们将确定AS是否会影响血糖和血压 在怀孕期间进行控制，并确定这些影响的潜在遗传易感基因。此外，我们还将 检测孕妇和新生儿全身炎症和血管内皮功能障碍的标志物 以前发现与暴露在更高暴露地区的成年人接触有关的疾病。我们的 假说是，怀孕和胎儿发育是对AS影响敏感的“窗口”。 对心脏代谢结果的影响。据我们所知，我们的研究是仅有的分子流行病学之一 年一般人群中易感人群的孕期和早期暴露于砷的调查 美国。心血管疾病是世界范围内发病率和死亡率的主要原因，也是其风险所在。 疾病在生命早期就开始了。因此，我们现在可以利用我们在上一次拨款中所做的工作 填补我们对早年接触AS对终身健康影响的理解方面的关键空白的时期，其中之一 令人担忧的主要环境化学品。

Project 4: Abstract Project 4, a biomedical project, is an integral component of the Dartmouth Superfund Research Program. Over the past 18 years, we designed and tested methods of measuring environmentally relevant levels of exposure to metals and applied novel biomarkers of exposure, susceptibility, and early response to large- scaled, population-based epidemiologic studies in the US. To date, we have tested over 8,000 households for arsenic (As), of which over 3,500 had private water systems. A GIS analysis of the data (performed in collaboration with the Trace Element Analysis Core) revealed distinct "clusters" of high household water As levels. Over the past five years, we successfully established a pregnancy cohort of women who use private wells in one of these cluster regions. Of the household tap water samples tested thus far, ~15% exceeded the maximum contaminant level for As established by the US EPA of 10 ¿g/L. Over the next five years, we will begin recruitment in another cluster region that is adjacent to planned and existing Superfund sites. While evidence suggests that As is related to adult onset diabetes and hypertension, its effects on these outcomes during pregnancy are uncertain. Thus, we will determine whether As influences glucose and blood pressure control during pregnancy and identify potential genetic susceptibility loci for these effects. Additionally, we will test pregnant women and newborns for markers of systemic inflammation and vascular endothelial dysfunction that have been previously found to relate to As exposure among adults in more highly exposed regions. Our hypothesis is that pregnancy and fetal development represent "windows" of susceptibility to the effects of As on cardiometabolic outcomes. To our knowledge, our study is one of the only molecular epidemiologic investigations of pregnancy and early life exposure to As in vulnerable subgroups of the general population of the US. Cardiovascular disease is the leading cause of morbidity and mortality worldwide, and the risk for this disease begins early in life. Thus, we are now positioned to capitalize upon our work in the previous grant period to fill critical gaps in our understanding of the lifelong health impacts of early life exposure to As, one of the leading environmental chemicals of concern.