Organochlorine exposure, genetic polymorphism and Parkinson's disease

描述(取自应用程序) 帕金森-S病(PD)是一种进行性的、致残的中枢神经系统疾病。 神经系统的特征是休息时震颤，肌肉僵硬，迟缓， 不平衡，在以后的阶段常常是痴呆症。这是由于损失了 黑质中产生多巴胺的神经元。大约半个月 据估计，有100万美国人受到帕金森病的影响。最近的数据表明 环境暴露，可能与基因决定的 脆弱性，导致帕金森病的原因；特别是在患有 发病年龄在50岁以上。这项研究将检查300例帕金森病患者，其 诊断已通过严格、标准化的标准和300 与未累及基底节的“轻微”神经障碍对照。一个 将获取血样，并将提供详细的调查问卷 对每个病例和对照进行管理。这些团体将一半是男性，一半是男性 女性。所有符合条件的少数族裔患者都将被纳入。病例和对照 将在年龄、性别和种族上相匹配。这项建议有两个相互关联的 以生物医学为基础的流行病学目标。我们建议确定：1) 无论血清有机氯水平和/或既往接触史 帕金森S病患者体内农药含量升高；2) 与农药代谢相关的特定酶的多态性更多 在帕金森病患者中常见；以及3)是否有证据表明存在基因环境 互动。更具探索性的目标是评估 饮食，尤其是抗氧化剂的摄入，可能会预防糖尿病的发生。 警察。为了检验有机氯水平的假设，最常见的类型 在1940年至1970年期间使用的化学农药的比例在帕金森州有所增加 患者的DDT、DDE、狄氏剂和环氧氯丹将被测定和比较 病例和对照之间的差异。多氯联苯、其同系物和反式橙花草胺也将 因为这些也是有机氯化合物，所以需要测量。基因 多态假设将特别集中在CYP2D6、GSTP1和PON1上。 为了评估抗氧化剂可能的保护作用，详细的饮食 我们将利用历史来获取有关常用抗氧化剂的广泛信息 诊断前的摄入量，包括维生素A，C和E，类胡萝卜素，番茄红素， 生育酚和多酚(植物雌激素)。

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).