Registry Study of Parkinsons Disease in Denmark

丹麦帕金森病登记研究

• 批准号: 7096783
• 负责人: Beate R Ritz
• 金额: $ 90.55万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-19 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7096783
• 关键词: Parkinson' s disease; Scandinavian country; agriculture worker; brain injury; clinical research; disease /disorder proneness /risk; drug adverse effect; environmental exposure; functional /structural genomics; gene environment interaction; genetic polymorphism; human data; human subject; inflammation; iron metabolism; longitudinal human study; medical complication; metals; nervous system disorder epidemiology; occupational hazard; patient /disease registry; patient oriented research; pesticides; solvents; trauma

DESCRIPTION (provided by applicant): Gene-environment interactions may be major contributors to Parkinson's disease (PD) etiology, however this area of research has been severely hampered by the relatively small sample size of most population-based PD studies and/or a lack of valid and standardized exposure assessment across studies. We will take advantage of a worldwide unique resource available in Denmark to conduct the largest population-based case-control study ever to examine gene-environment interactions in PD: the National Parkinson's Patient Register in Denmark. We propose to recruit actively and prospectively approximately 2500 recently registered incident PD patients and 2,500 age-gender matched controls from the Danish population to collect risk factor information per interview and biological materials for genetic analyses. All patients will be examined and characterized clinically and phenotypically by a trained movement disorder fellow. We will examine 1) which lifetime occupations and occupational exposures are associated with PD; specifically, we will evaluate farming and greenhouse occupations (pesticides), metal related industries (metals and solvents), and night shift work (melatonin levels); 2) whether certain drugs and medical conditions are positively or inversely associated with PD (e.g. NSAIDS, aspirin, and cortisone use, or M. Crohn and colitis and rheumatoid arthritis) through their potential to induce chronically low iron levels and induce/reduce systemic inflammation; and 3) previously identified factors including smoking, alcohol use, dietary nutrients and contaminants (such as pesticides and metals from fish consumption), and physical activity. Most importantly, we will examine whether functional polymorphisms of metabolic and PD specific candidate genes differentially influence risks associated with environmental factors. As a secondary aim we will also employ passive record linkage by unique ID to link data from the National Patient Register, Pharmacy Database, and National Pension fund to identify risk factor information contained in these records (e.g. occupations, medication use, and diseases prior to PD onset) for approximately 13,000 PD cases diagnosed since 1983 and age-gender matched controls from the Danish population. The proposed research cannot be performed in the US due to a lack of population PD registries that would provide access to such a large number of cases and valid methods for control recruitment from the general population.

描述（由申请人提供）：基因-环境相互作用可能是帕金森病 (PD) 病因学的主要贡献者，然而，由于大多数基于人群的 PD 研究样本量相对较小和/或缺乏，该领域的研究受到严重阻碍。跨研究的有效且标准化的暴露评估。我们将利用丹麦的全球独特资源，开展迄今为止最大规模的基于人群的病例对照研究，以检查帕金森病中基因与环境的相互作用：丹麦国家帕金森病患者登记册。我们建议从丹麦人群中积极前瞻性地招募约 2500 名最近登记的帕金森病患者和 2500 名年龄性别匹配的对照组，以收集每次访谈的危险因素信息和用于遗传分析的生物材料。所有患者都将由训练有素的运动障碍研究员进行检查并进行临床和表型表征。我们将检查 1) 哪些终生职业和职业暴露与帕金森病相关；具体来说，我们将评估农业和温室职业（农药）、金属相关行业（金属和溶剂）以及夜班工作（褪黑激素水平）； 2) 某些药物和医疗状况是否与帕金森病呈正相关或负相关（例如非甾体抗炎药、阿司匹林和可的松的使用，或克罗恩分枝杆菌与结肠炎和类风湿性关节炎）是否有可能诱发慢性低铁水平并诱发/减少全身炎症; 3) 先前确定的因素包括吸烟、饮酒、饮食营养素和污染物（例如来自鱼类消费的杀虫剂和金属）以及体力活动。最重要的是，我们将检查代谢和 PD 特异性候选基因的功能多态性是否对与环境因素相关的风险产生不同的影响。作为次要目标，我们还将采用通过唯一 ID 的被动记录链接来链接来自国家患者登记册、药房数据库和国家养老金基金的数据，以识别这些记录中包含的风险因素信息（例如职业、药物使用和疾病之前）自 1983 年以来诊断出的约 13,000 例 PD 病例以及来自丹麦人群的年龄性别匹配对照。拟议的研究无法在美国进行，因为缺乏人口 PD 登记处，无法提供大量病例和控制从普通人群招募的有效方法。