Epidemiology of Dystonia in a Multi-Ethnic Population

多民族人群肌张力障碍的流行病学

• 批准号: 6976884
• 负责人: Caroline M. Tanner
• 金额: $ 100.4万
• 依托单位: PARKINSON'S INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6976884
• 关键词: age difference; body physical activity; clinical research; data collection methodology /evaluation; disease /disorder classification; disease /disorder onset; dystonia; family genetics; gender difference; gene environment interaction; gene mutation; genetic disorder diagnosis; genetic susceptibility; genotype; high performance liquid chromatography; human genetic material tag; human subject; infection; interview; nervous system disorder diagnosis; nervous system disorder epidemiology; occupational hazard; questionnaires; racial /ethnic difference; smoking; trauma

DESCRIPTION (provided by applicant): Dystonia is a disabling neurodegenerative disease that causes sustained involuntary muscle contractions, producing twisting, repetitive and patterned movements or abnormal postures. While it is the third most common movement disorder, little is known about ethnic or racial variation in the occurrence of dystonia or about risk factors. To address this problem, we will establish a dystonia incident cohort identified from among approximately 3 million individuals in a large, multiethnic (~40% non-white) health maintenance organization. We expect to identify at least 1000 incident cases of primary torsion dystonia (PTD). This will constitute by far the largest population of PTD patients ever enrolled in an epidemiologic study and will provide the foundation for addressing, for the first time, a number of questions regarding the epidemiology of dystonia. The first aim of this application is to estimate the incidence and prevalence of PTD overall and for clinically-defined subtypes (including generalized, cranial, cervical, limb and laryngeal dystonias). Incidence and prevalence within groups will be estimated by age, gender and race/ethnicity. This will be the first epidemiologic study of PTD of all types in a racially and ethnically diverse population. The second aim will be to investigate familial aggregation of dystonia in cases and controls, as measured by validated family history interviews, and to determine if this varies by subtype of dystonia and ethnicity. The third aim is to determine the frequency of the DYT1 mutation, associated with PTD, within groups defined by ethnicity and clinical features. Aim 4 is to investigate the role of environmental exposures that may influence the expression of dystonia and the penetrance of the known gene (DYT1), including specific antecedent health events (trauma, infection) or lifestyle factors (occupation, hobbies, cigarette smoking, physical activity) by comparing the frequency of these events before dystonia onset in cases and approximately 1000 matched controls. This will be the first investigation of the incidence, prevalence, and associated risk factors of PTD in-a large unselected multiethnic population. It will be the largest population of PTD ever studied epidemiologically. Advantages of the study setting include: (1) it is demographically similar to the underlying population of northern California, (2) access to care is unrestricted, reducing biased ascertainment, (3) a large control population is available and (4) certain health-related risk factors can be identified through computerized records, minimizing recall bias. These investigations have the potential to provide significant insights into the determinants of dystonia. In addition, this cohort will provide a rich resource for future investigations including family studies, genetic analyses and further investigations of environmental risk factors.

描述（由申请人提供）：肌张力障碍是一种致残性神经退行性疾病，会导致持续的不自主肌肉收缩，产生扭曲、重复和模式化的运动或异常姿势。虽然它是第三种最常见的运动障碍，但人们对肌张力障碍发生的种族差异或危险因素知之甚少。为了解决这个问题，我们将建立一个肌张力障碍事件队列，该队列是从一个大型多种族（约 40% 非白人）健康维护组织中约 300 万人中确定的。我们预计将识别出至少 1000 例原发性扭转肌张力障碍 (PTD) 病例。这将构成迄今为止参加流行病学研究的最大 PTD 患者群体，并将首次为解决有关肌张力障碍流行病学的许多问题奠定基础。该应用程序的首要目的是估计 PTD 的总体发生率和患病率以及临床定义的亚型（包括全身肌张力障碍、颅肌肌张力障碍、颈肌肌张力障碍、四肢肌张力障碍和喉肌肌张力障碍）。群体内的发病率和患病率将根据年龄、性别和种族/民族进行估计。这将是第一个针对不同种族和族裔人群的所有类型 PTD 的流行病学研究。第二个目标是调查病例和对照中肌张力障碍的家族聚集情况，通过经过验证的家族史访谈进行测量，并确定这种情况是否因肌张力障碍亚型和种族而异。第三个目标是确定由种族和临床特征定义的群体内与 PTD 相关的 DYT1 突变的频率。目标 4 是研究可能影响肌张力障碍表达和已知基因 (DYT1) 外显率的环境暴露的作用，包括特定的既往健康事件（创伤、感染）或生活方式因素（职业、爱好、吸烟、身体状况）。通过比较病例和大约 1000 名匹配对照者肌张力障碍发作前这些事件的频率。这将是首次在大量未经选择的多种族人群中对 PTD 的发病率、患病率和相关危险因素进行调查。这将是有史以来流行病学研究中最大规模的 PTD 人群。研究环境的优点包括：(1) 在人口统计学上与北加州的基础人口相似，(2) 获得护理的机会不受限制，减少了有偏见的确定，(3) 有大量对照人群，(4) 具有一定的健康状况相关的风险因素可以通过计算机记录来识别，最大限度地减少回忆偏差。这些研究有可能为肌张力障碍的决定因素提供重要的见解。此外，该队列将为未来的研究提供丰富的资源，包括家庭研究、遗传分析和环境风险因素的进一步研究。