Skin Pigmentation and Parkinson's Disease Risk

皮肤色素沉着和帕金森病风险

• 批准号: 6480198
• 负责人: Caroline M. Tanner
• 金额: $ 19.41万
• 依托单位: PARKINSON'S INSTITUTE
• 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 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6480198
• 关键词: Parkinson's disease; agriculture worker; calorimetry; clinical research; disease /disorder proneness /risk; human subject; melanins; pesticide biological effect; pigmentation

DESCRIPTION (provided by applicant): The goal of this proposal is to investigate the relationship between skin pigmentation and Parkinson's disease (PD). Early clinical and epidemiologic observations suggested that PD might be most common in persons of European origin. A biologically plausible explanation for this observation emerged in 1983 when the Parkinsonism-causing toxicant MPTP was identified. The toxic form of this compound, MPP+, was shown to bind to neural melanin; leading to the proposal that dermal melanin may "protectively" bind potential neurotoxicants and prevent their entry into the brain. This possibility is further supported by the observation that dermal melanin selectively binds reactive species (free radicals). Preliminary data suggests that persons with greater tendency to sunburn and persons with lighter skin tone as measured by calorimetry are at greater risk of PD. We propose to confirm (or refute) this observation by investigating the relationship between skin color (which directly correlates with dermal melanin concentration) and risk of PD in a unique human population of farmers in the Agricultural Health Study (AHS). The AHS includes approximately 52,000 pesticide applicators and 32,000 of their spouses, living in Iowa and North Carolina for who detailed life histories of exposures to specific pesticides and direct exposure measurements have been collected. The cohort was enrolled in 1994-96, at which time information was collected on pesticide use, other farming practices, and life-style and health, including Parkinson's disease. FAME is an NIH-funded nested case-control study within the AHS comparing persons with Parkinson's disease to controls is in progress. The current proposal will take advantage of this unique resource to investigate the hypothesis that dermal melanin protects against Parkinson's disease. Skin pigmentation will be measured directly using tristimulus calorimetry during on the farm visits. Standardized and validated questions will be used to assess complexion, hair color, and tendency to sunburn. Lighter complexion and lighter hair color (blond, red) and greater tendency to sunburn are expected to be associated with increased risk of PD. We expect to identify 160 Parkinson's disease cases and 3 controls per case in FAME. Data analysis will utilize univariate and multivariate likelihood-based methods for matched case-control studies. If less skin pigmentation, alone or in combination with other risk factors, is shown to increase PD risk, this will suggest a role for melanin in the pathogenesis of PD. This could be an enormous breakthrough in our understanding of factors that influence the risk (and perhaps even the cause) of Parkinson's disease, and could lead to new strategies for disease prevention.

描述（申请人提供）：该提案的目的是 研究皮肤色素沉着与帕金森氏病之间的关系 （PD）。早期临床和流行病学观察结果表明PD可能是 最常见的是欧洲血统的人。生物学上合理的解释 对于这种观察到1983年，当时帕金森主义引起毒性 确定了MPTP。该化合物MPP+的有毒形式已显示为结合 致神经黑色素；导致皮肤黑色素可能 “保护性”结合潜在的神经毒性，并防止其进入 脑。真皮的观察进一步支持了这种可能性 黑色素选择性结合反应性物种（自由基）。初步数据 表明有更大倾向于晒伤和更轻的人的人 通过量热法测量的肤色面临PD的更大风险。我们建议 通过研究（或驳斥）通过研究 肤色（与真皮黑色素浓度直接相关）和 在农业健康中，独特的农民人口中PD的风险 研究（AHS）。 AHS包括大约52,000名农药施用者和 他们的配偶中有32,000人居住在爱荷华州和北卡罗来纳州 暴露于特定农药和直接暴露的生活史 已经收集了测量。该队列于1994 - 96年招收 收集有关农药使用，其他农业实践和的时间信息 生活方式和健康，包括帕金森氏病。名望是NIH资助的 AHS中的嵌套案例对照研究与帕金森氏症的人进行了比较 对照疾病正在进行中。当前的建议将利用 这种独特的资源来研究真皮黑色素保护的假设 反对帕金森氏病。皮肤色素沉着将直接使用 在农场探访期间的三角肌量热法。标准化和验证 问题将用于评估肤色，发色和倾向 晒斑。浅色和较轻的头发颜色（金色，红色）和更大 预计晒伤的趋势与PD风险增加有关。我们 期望确定160例帕金森氏病病例和3例对照 名望。数据分析将利用单变量和基于多变量的可能性 匹配的病例对照研究的方法。如果皮肤色素沉着少，单独或 结合其他危险因素，证明会增加PD风险，这将 提出黑色素在PD发病机理中的作用。这可能是巨大的 我们对影响风险的因素的理解的突破（以及 也许甚至是帕金森氏病的原因，并且可能导致新的 预防疾病的策略。