Skin Pigmentation and Parkinson's Disease Risk

描述（由申请人提供）：本提案的目标是 研究皮肤色素沉着与帕金森病的关系 （PD）。早期的临床和流行病学观察表明，PD可能是 最常见于欧洲血统的人。从生物学角度来说 1983年，导致帕金森症的毒物 MPTP已确定。这种化合物的毒性形式MPP+被证明可以结合 神经黑色素;导致皮肤黑色素可能 “保护性”地结合潜在的神经毒物，并防止它们进入神经系统。 个脑袋这种可能性进一步得到以下观察结果的支持： 黑色素选择性地结合活性物质（自由基）。初步数据 这表明，那些更容易晒伤的人和那些皮肤较浅的人， 通过量热法测量肤色具有更大的PD风险。我们建议 通过调查以下两种情况之间的关系来证实（或反驳）这一观察结果： 皮肤颜色（与皮肤黑色素浓度直接相关）， 在农业健康中，一个独特的农民人群中的PD风险 研究（AHS）。AHS包括大约52，000个农药施用器， 32,000名居住在爱荷华州和北卡罗来纳州的配偶， 接触特定农药和直接接触的生活史 测量已经收集。该队列于1994-96年入组， 时间信息收集农药的使用，其他农业实践， 生活方式和健康，包括帕金森病。FAME是NIH资助的 在AHS中进行的一项比较帕金森患者的巢式病例对照研究 疾病控制正在进行中。目前的提案将利用 这一独特的资源，以调查假设，皮肤黑色素保护 对抗帕金森病。皮肤色素沉着将直接使用 参观农场期间的三刺激量热法。标准化和验证 问题将用于评估肤色，头发颜色和倾向， 晒伤了肤色较浅，头发颜色较浅（金色，红色）， 晒伤倾向与PD风险增加有关。我们 预计将确定160例帕金森病病例和3例对照， 名人数据分析将使用基于单变量和多变量可能性的 配对病例对照研究的方法。如果皮肤色素沉着少，单独或 与其他风险因素结合，显示会增加PD风险，这将 提示黑色素在PD发病机制中的作用。这可能是一个巨大的 我们对影响风险因素的理解的突破（以及 甚至可能是帕金森病的原因），并可能导致新的 疾病预防战略。

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.