Relationship of Blood Esterases, Pesticide Exposure and Cardiovascular Disease

描述(由申请者提供)：本次R21拨款申请旨在巩固密西西比州立大学环境健康科学中心基础和临床研究人员的跨学科团队，研究导致南方腹地和非裔美国人心血管疾病(CVD)死亡率较高的环境因素，并使该团队能够参与正在进行的更大规模的多机构流行病学研究。心血管疾病的这种健康差距在逻辑上与南方更普遍的风险因素有关(那里的非裔美国人比例高于该国其他地区)。南方是农村，农业高度发达，因此预计南方人口经常会接触到比许多其他地区更高水平的杀虫剂。我们假设如下：农药暴露的影响有助于心血管疾病的发展，并且在非裔美国人中更加明显。我们多年来一直研究的两种酶是对氧磷酶(PON1)和羧酸酯酶(CAE)，因为它们参与了许多农药的解毒。已知前者与高密度脂蛋白颗粒有关，后者最近被确定为参与胆固醇反向运输的胆固醇酯水解酶；因此，这两种酶都与血管健康有关，是心血管疾病易感性的潜在生物标志物。我们有经验将尿液中的农药代谢物作为当前农药暴露的一个指标。我们开发了一种新的农药收获作物记录的地理空间分析，可以预测个人在过去35年的生活中接触到农药。我们在心脏病学方面有经验，并在心脏病学实践中接触到患者。我们建议进行一项先导性研究，以调查从心脏病实践中招募的受试者的上述参数(即血液中的PON1和尿液中的农药代谢物)，并计算这些因素、心血管疾病程度和地理空间分析模型中估计的农药暴露之间的关联强度。这项试点研究将在经过一年的规划、巩固跨学科团队、优化分析并发展与项目顾问的互动之后进行。这项初步研究将使我们能够通过与阿拉巴马大学伯明翰分校的顾问互动，参与一项更广泛的研究。此外，我们预计我们将开发更简单的PON1和CAE检测方法，更适合作为临床生物标志物使用。

DESCRIPTION (provided by applicant): This application for an R21 grant is designed to solidify an interdisciplinary team of basic and clinical researchers in the Center for Environmental Health Sciences at Mississippi State University for research into the environmental factors contributing to the higher mortality of cardiovascular disease (CVD) in the Deep South and among African Americans, and to position this team for participation in larger-scale on- going multi-institutional epidemiological studies. This health disparity in CVD is logically related to risk factors more prevalent in the South (which has a higher proportion of African Americans than other regions in the country.) The South is rural and highly agricultural, so the Southern populations would be expected to be routinely exposed to higher levels of pesticides than populations in many other regions. We hypothesize the following: The effects of pesticide exposure contribute to the development of CVD and are more pronounced in the African American population. Two enzymes that we have studied for many years because of their involvement in the detoxication of many pesticides are paraoxonase (PON1) and carboxylesterase (CaE). The former is known to be associated with HDL particles and the latter has recently been identified as a cholesteryl ester hydrolase that is involved in reverse cholesterol transport; therefore, both of these enzymes are involved in vascular health, and are potential biomarkers of susceptibility to CVD. We have experience biomonitoring urinary pesticide metabolites as an index of current pesticide exposure. We have developed a novel geospatial analysis of pesticide harvested crop records that predicts pesticide exposure to individuals for the previous 35 years of their lives. We have experience in cardiology and access to patients in a cardiology practice. We propose a pilot study to investigate the above listed parameters (i.e., PON1 and CaE in the blood and pesticide metabolites in the urine) of subjects recruited from the cardiology practice, and to calculate strength of associations among these factors, the degree of cardiovascular disease and the pesticide exposure estimated in the geospatial analysis model. This pilot study will be conducted following a year of planning, solidifying the interdisciplinary team, optimizing assays, and developing interactions with the project's consultants. The pilot study will position us to participate in a far more extensive study through interactions with our consultants at the University of Alabama at Birmingham. In addition, we anticipate that we will develop more simplified assay methods for PON1 and CaE that will be more amenable for use as a clinical biomarker.