Skin Pigmentation and Parkinson's Disease Risk

描述(由申请人提供)：本提案的目标是 皮肤色素沉着与帕金森病关系的研究 (Pd)。早期的临床和流行病学观察表明帕金森病可能是 最常见的是欧洲血统的人。生物学上看似合理的解释 这一观察结果出现在1983年，当时导致帕金森症的毒剂 对MPTP进行鉴定。这种化合物的有毒形式MPP被证明能结合 神经黑色素；导致了皮肤黑色素可能 “保护性”地结合潜在的神经毒物，防止它们进入 大脑。这种可能性进一步得到了以下观察的支持：皮肤病 黑色素选择性地结合活性物质(自由基)。初步数据 表明有较大晒伤倾向的人和有较轻晒伤倾向的人 用热量计测量的肤色有更大的患帕金森病的风险。我们建议 通过调查两者之间的关系来证实(或驳斥)这一观察 肤色(与皮肤黑色素浓度直接相关)和 农业卫生中特殊人群中帕金森病风险的研究 研究(AHS)。AHS包括大约52,000个杀虫剂施用者和 他们的32,000名配偶，居住在爱荷华州和北卡罗来纳州，世卫组织详细介绍了 接触特定农药和直接接触的生活史 已经收集了测量数据。该队列是在1994-96年间招募的，当时 收集了关于杀虫剂使用、其他耕作方法和 生活方式和健康，包括帕金森氏症。名气是由美国国立卫生研究院资助的 AHS患者与帕金森病患者的嵌套病例对照研究 疾病向控制措施的转移正在进行中。目前的提案将利用 这一独特的资源来研究皮肤黑色素保护的假说 治疗帕金森氏症。皮肤色素沉着将直接使用 在农场参观期间的三刺激量热法。标准化和经验证 问题将被用来评估肤色、发色和倾向 晒伤。较浅的肤色和较浅的头发颜色(金色、红色)和更深 晒伤的倾向预计与帕金森病风险的增加有关。我们 预计在#年确定160例帕金森氏症病例和3例对照 名声。数据分析将利用基于单变量和多变量似然的方法 配对病例对照研究方法。如果皮肤色素沉着较少，单独或 与其他危险因素相结合，显示会增加帕金森病的风险，这将 提示黑色素在帕金森病发病机制中的作用。这可能是一个巨大的 我们对影响风险的因素的理解取得了突破(和 也许甚至是帕金森氏症的原因)，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.