Organochlorine exposure, genetic polymorphism and Parkinson's disease

有机氯暴露、遗传多态性与帕金森病

• 批准号: 6578820
• 负责人: Gertrud S. Berkowitz
• 金额: $ 8.37万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6578820
• 关键词: Parkinson's disease; antioxidants; blood chemistry; chlorohydrocarbon; chlorohydrocarbon insecticide; dichlorodiphenyltrichloroethane; diet; environmental contamination; environmental exposure; environmental toxicology; gene environment interaction; genetic polymorphism; halobiphenyl /halotriphenyl compound; human subject; patient oriented research; pesticides; questionnaires

DESCRIPTION (Taken from application) Parkinson?s disease (PD) is a progressive, disabling disorder of the central nervous system characterized by tremors at rest, muscle rigidity, slowness, imbalance and, in later stages, often dementia. It is caused by loss of neurons in the substantial nigra that produce dopamine. Approximately half a million Americans are estimated to be affected by PD. Recent data suggest that environmental exposure, possibly in concert with genetically determined vulnerabilities, contribute to causation of PD; particularly in patients with onset of disease above age 50. The study will examine 300 cases of PD whose diagnoses have been confirmed by strict, standardized criteria and 300 controls with "minor" neurologic disorders not involving the basal ganglia. A blood sample will be obtained and a detailed questionnaire will be administered to each case and control. The groups will be half male, half female. All eligible minority patients will be enrolled. Cases and controls will be matched on age, gender, and race. This proposal has two inter-related biomedically based, epidemiologic objectives. We propose to determine: 1) whether serum organochlorine levels and/or a past history of exposure to pesticides are elevated in patients with Parkinson s disease; 2) whether polymorphisms in specific enzymes related to pesticide metabolism are more common in patients with PD; and 3) whether there is evidence for a gene-environment interaction. A more exploratory objective is to evaluate whether diet, particularly intake of antioxidants, may protect against development of PD. To test the hypothesis that organochlorine levels, the most common type of chemical pesticide used between 1940 and 1970, are increased in PD patients, DDT, DDE, Dieldrin, and oxychlordane will be determined and compared between cases and controls. PCB, its congeners and trans-nonachlor will also be measured since these are organochlorine compounds as well. The gene polymorphism hypotheses will focus specifically on CYP2D6, GSTP1, and PON1. To evaluate the possible protective role of antioxidants, a detailed dietary history will be taken to obtain extensive information on usual antioxidant intake before diagnosis, including Vitamins A, C and E, carotenoids, lycopene, tocopherol and polyphenols (phytoestrogens).

描述（摘自应用程序） 帕金森？帕金森病（PD）是一种进行性的中枢神经系统功能障碍， 神经系统的特点是在休息时颤抖，肌肉僵硬，缓慢， 不平衡，并在后期阶段，往往痴呆症。它是由失去 黑质中产生多巴胺的神经元。大约半 据估计，有100万美国人受到PD的影响。最近的数据表明 环境暴露，可能与基因决定的 脆弱性，有助于PD的病因;特别是在患者中， 50岁以上发病。该研究将检查300例PD病例， 诊断已通过严格、标准化的标准和300 不涉及基底神经节的“轻微”神经系统疾病的对照组。一 将获得血液样本，并将进行详细的问卷调查。 给每例病例和对照组施用。每组一半是男性，一半是 女性所有合格的少数民族患者都将入组。病例和对照 将根据年龄性别和种族进行匹配该提案有两个相互关联的 基于生物医学的流行病学目标。我们建议确定：1） 血清有机氯水平和/或过去接触过 帕金森病患者的农药含量升高; 2）是否 与农药代谢相关的特定酶的多态性更多 常见于PD患者; 3）是否有证据表明基因环境 互动一个更具探索性的目标是评估是否 饮食，特别是摄入抗氧化剂，可以防止发展， 警局为了验证有机氯含量的假设，最常见的类型 1940年至1970年期间使用的化学农药， 患者，DDT，DDE，狄氏剂和氧氯噻嗪将被测定和比较 病例组和对照组之间的差异多氯联苯、其同系物和反式九氯草胺也将 因为它们也是有机氯化合物。基因 多态性假说将特别关注CYP 2D 6、GSTP 1和PON 1。 为了评估抗氧化剂可能的保护作用， 将记录历史以获取有关常用抗氧化剂的广泛信息 诊断前摄入的维生素A、C和E、类胡萝卜素、番茄红素， 生育酚和多酚（植物雌激素）。