Relationship of Blood Esterases, Pesticide Exposure and Cardiovascular Disease

描述（申请人提供）：R21补助金的申请旨在巩固密西西比州立大学环境健康科学中心的基础和临床研究人员的跨学科团队，以研究导致南方腹地和非洲裔美国人心血管疾病（CVD）死亡率较高的环境因素，并使该小组能够参与更大规模的正在进行的多机构流行病学研究。心血管疾病的这种健康差异在逻辑上与南方更普遍的风险因素有关（南方的非洲裔美国人比例高于该国其他地区）。南方是农村地区，高度农业化，因此预计南方人口通常会比许多其他地区的人口接触更高水平的农药。我们假设如下：农药暴露的影响有助于心血管疾病的发展，在非洲裔美国人中更为明显。对氧磷酶（PON 1）和羧酸酯酶（CaE）是我们研究多年的两种酶，因为它们参与许多农药的解毒。已知前者与HDL颗粒相关，后者最近被鉴定为参与胆固醇逆向转运的胆固醇酯水解酶;因此，这两种酶都参与血管健康，并且是CVD易感性的潜在生物标志物。我们有经验的生物监测尿农药代谢物作为当前农药暴露的指标。我们开发了一种新的农药收获作物记录的地理空间分析，预测个人在过去35年中的农药暴露。我们在心脏病学方面拥有丰富的经验，并在心脏病学实践中接触到患者。我们提出了一项试点研究，以调查上述参数（即，血液中的PON 1和CaE以及尿液中的农药代谢物），并计算这些因素之间的关联强度，心血管疾病的程度和地理空间分析模型中估计的农药暴露。这项试点研究将在经过一年的规划、巩固跨学科团队、优化分析以及与项目顾问开展互动后进行。试点研究将使我们能够通过与我们在伯明翰亚拉巴马大学的顾问进行互动，参与一项更为广泛的研究。此外，我们预计我们将开发更简化的PON 1和CaE检测方法，这些方法更适合用作临床生物标志物。

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.