Organochlorine pesticide, PCBs, and Parkinsons

有机氯农药、多氯联苯和帕金森病

• 批准号: 7101808
• 负责人: ALBERTO ASCHERIO
• 金额: $ 34.16万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7101808
• 关键词: Parkinson' s disease; Scandinavian country; biomarker; blood tests; chlorohydrocarbon insecticide; clinical research; dichlorodiphenyltrichloroethane; disease /disorder proneness /risk; environmental exposure; halobiphenyl /halotriphenyl compound; hazardous substances; human data; human tissue; longitudinal human study; neuroprotectants; occupational hazard; pesticide biological effect; questionnaires; urate

DESCRIPTION (provided by applicant): We propose to study prospectively whether the risk of Parkinson's disease (PD) is predicted by plasma levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), and the antioxidant uric acid. The proposed investigation will take advantage of a unique population comprising over 35,000 Finnish men and women who provided blood samples in 1968-72 as part of a health examination survey, and have subsequently been followed for incidence of PD for over 20 years. Between the baseline survey and 1994, 201 new cases of PD have been confirmed in this population. Plasma levels of organochlorine insecticides, PCBs, and uric acid will be assessed among these cases and controls matched by age and gender. Specific hypotheses to be tested include: 1) That higher plasma levels of para, para-dichlorodiphenyl dichloroethene [p,p-DDE], the major metabolite of DDT, dieldrin, hexachlorobenzene (HCB), beta-hexachlorocyclohexane (HCH), heptachlor, heptachlor epoxide, trans-nonachlor, and oxychlordane are associated with increase risk of PD; 2) that higher plasma levels of PCBs (sum of all congeners) are associated with an increased risk of PD; and 3) that higher plasma levels of the antioxidant uric acid are associated with a decreased risk of PD, and exert a protective effect against the deleterious effects of DDE. The proposed investigation is unique and innovative as there are no previous data relating biomarkers of exposure to environmental contaminants and future risk of developing PD. The blood samples were collected at a time of high exposure to both organochlorine insecticides and PCBs as supported by the high mean plasma level of DDE and PCBs that we found in a pilot study. Finally, the long follow-up period will allow the investigation of long-term effects of exposure.

描述（由申请人提供）：我们建议前瞻性研究帕金森病（PD）的风险是否可以通过有机氯农药、多氯联苯（PCB）和抗氧化剂尿酸的血浆水平来预测。拟议的调查将利用由超过 35,000 名芬兰男性和女性组成的独特人群，他们在 1968-72 年期间提供了血液样本，作为健康检查调查的一部分，并随后对 PD 发病率进行了 20 多年的跟踪。从基线调查到 1994 年，该人群中已确诊 201 例新的 PD 病例。将根据年龄和性别对这些病例和对照人群中有机氯杀虫剂、多氯联苯和尿酸的血浆水平进行评估。待检验的具体假设包括： 1) 对，对二氯二苯基二氯乙烯 [p,p-DDE]（DDT 的主要代谢物）、狄氏剂、六氯苯 (HCB)、β-六氯环己烷 (HCH)、七氯、环氧七氯、反式九氯和氯丹与帕金森病风险增加有关； 2) 血浆中多氯联苯（所有同系物的总和）水平较高与帕金森病风险增加相关； 3) 抗氧化剂尿酸的血浆水平较高与 PD 风险降低相关，并对 DDE 的有害作用发挥保护作用。拟议的调查是独特和创新的，因为之前没有关于暴露于环境污染物的生物标志物和未来患帕金森病的风险的数据。血液样本是在大量接触有机氯杀虫剂和 PCB 时采集的，我们在一项试点研究中发现 DDE 和 PCB 平均血浆水平较高，这证明了这一点。最后，较长的随访期将允许调查暴露的长期影响。