Relationship of Blood Esterases, Pesticide Exposure and Cardiovascular Disease

血酯酶、农药暴露与心血管疾病的关系

• 批准号: 7906342
• 负责人: Janice Elaine Chambers
• 金额: $ 24.76万
• 依托单位: MISSISSIPPI STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-04 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7906342
• 关键词: African American; Agriculture; Agrochemicals; Alabama; Arterial Fatty Streak; Arylesterase; Beds; Bile fluid; Biochemical; Biological Assay; Biological Markers; Biological Monitoring; Blood; Blood Vessels; Blood specimen; Carboxylic Ester Hydrolases; Cardiology; Cardiovascular Diseases; Cardiovascular system; Characteristics; Cholesterol; Cholesterol Esters; Clinic; Clinical; Clinical Research; Clinical Trials; Communication; Coronary Arteriosclerosis; Country; County; Data; Data Set; Deep South; Detection; Development; Diagnosis; Disease; Doctor of Philosophy; Economics; Educational Background; Environmental Health; Environmental Risk Factor; Enzymes; Epidemiologic Studies; Epidemiologist; Epidemiology; Etiology; Evaluation; Excretory function; Exposure to; Faculty; Farming environment; Genetic Polymorphism; Grant; Harvest; Health; High Density Lipoproteins; Hospitals; Human; Hydrolysis; Individual; Insecticides; Interdisciplinary Study; Intervention; Isoenzymes; Knowledge; Laboratories; Laboratory Animals; Life; Liver; Medical center; Methods; Mississippi; Modeling; Monitor; Organophosphates; Outcome; Patients; Pesticides; Phenotype; Physicians; Pilot Projects; Population; Positioning Attribute; Poverty; Predisposition; Prevalence; Principal Investigator; Questionnaires; Records; Recruitment Activity; Research; Research Personnel; Research Project Grants; Risk Factors; Role; Rural; Rural Hospitals; Sampling; Scientist; Socioeconomic Status; Stroke; Study Subject; Transport Process; United States; Universities; Urine; Visit; aryldialkylphosphatase; base; carboxylesterase; design; detoxication; diagnostic catheterization; esterase; experience; health disparity; indexing; interest; member; mortality; novel; organophosphorus insecticide; oxidized low density lipoprotein; particle; pesticide exposure; programs; racial difference; reverse cholesterol transport; tool; urinary

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.

描述（由申请人提供）：本 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的基础和临床研究人员的跨学科团队，以研究导致心血管疾病死亡率较高的环境因素（CVD）在南方腹地和非裔美国人中，并使该团队能够参与更大规模、正在进行的多机构流行病学研究。从逻辑上讲，CVD 的这种健康差异与南方更普遍的危险因素有关（该地区非裔美国人的比例高于该国其他地区）。南方是农村地区，农业高度发达，因此预计南方人口与许多其他地区的人口相比，他们经常接触到更高水平的农药。我们做出以下假设：接触农药的影响会导致心血管疾病的发生，并且在非裔美国人中更为明显。对氧磷酶 (PON1) 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。已知前者与高密度脂蛋白颗粒有关，后者最近被鉴定为参与胆固醇反向转运的胆固醇酯水解酶；因此，这两种酶都与血管健康有关，并且是 CVD 易感性的潜在生物标志物。我们拥有生物监测尿液农药代谢物作为当前农药暴露指标的经验。我们开发了一种新颖的农药收获作物记录地理空间分析方法，可以预测个体在过去 35 年中接触农药的情况。我们在心脏病学方面拥有丰富的经验，并且能够接触心脏病学实践中的患者。我们提出一项初步研究，以调查从心脏病学实践中招募的受试者的上述参数（即血液中的 PON1 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、心血管疾病的程度以及地理空间分析模型中估计的农药暴露量。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建立互动之后进行。该试点研究将使我们能够通过与伯明翰阿拉巴马大学顾问的互动参与更广泛的研究。此外，我们预计将为 PON1 和 CaE 开发更简化的测定方法，更适合用作临床生物标志物。

项目成果

Human paraoxonase 1 hydrolysis of nanomolar chlorpyrifos-oxon concentrations is unaffected by phenotype or Q192R genotype.

人对氧磷酶 1 水解纳摩尔毒死蜱浓度不受表型或 Q192R 基因型的影响。

• 发表时间: 2014-10-01
• 影响因子: 3.5
• 作者: Coombes, R Hunter;Meek, Edward C;Dail, Mary Beth;Chambers, Howard W;Chambers, Janice E
• 通讯作者: Chambers, Janice E

Paraoxonase 1 polymorphisms within a Mississippi USA population as possible biomarkers of enzyme activities associated with disease susceptibility.

美国密西西比州人群中的对氧磷酶 1 多态性可能是与疾病易感性相关的酶活性的生物标志物。

• 发表时间: 2014-12
• 影响因子: 2.4
• 作者: McDaniel, Chiquita Y;Dail, Mary Beth;Wills, Robert W;Chambers, Howard W;Chambers, Janice E
• 通讯作者: Chambers, Janice E

Racial differences in paraoxonase-1 (PON1): a factor in the health of southerners?

对氧磷酶 1 (PON1) 的种族差异：南方人健康的一个因素？

• 发表时间: 2009-08
• 影响因子: 10.4
• 作者: Davis, Kimberly A;Crow, J Allen;Chambers, Howard W;Meek, Edward C;Chambers, Janice E
• 通讯作者: Chambers, Janice E

Relationship of human paraoxonase-1 serum activity and genotype with atherosclerosis in individuals from the Deep South.

人类对氧磷酶 1 血清活性和基因型与南方腹地个体动脉粥样硬化的关系。

• 发表时间: 2011-12
• 作者: Coombes, R Hunter;Crow, J Allen;Dail, MaryBeth;Chambers, Howard W;Wills, Robert W;Barry D. Bertolet for CARe;Chambers, Janice E
• 通讯作者: Chambers, Janice E

The association of serum trans-nonachlor levels with atherosclerosis.

血清反式九氯水平与动脉粥样硬化的关联。

• 发表时间: 2016
• 作者: Mangum, Lee C;Mangum, Lauren H;Chambers, Janice E;Ross, Matthew K;Meek, Edward C;Wills, Robert W;Crow, J Allen
• 通讯作者: Crow, J Allen