A Prospective Study of Nicotine from Edible Solanaceae and Risk of Parkinson Disease

 描述(申请人提供)：帕金森病(PD)是美国第二常见的神经退行性疾病，影响着100多万美国人；由于人口老龄化，这个数字还在增长。大多数患者最终发展为严重残疾，这显著影响了他们和他们的照顾者的生活质量。因此，迫切需要开发疾病修正或神经保护疗法。在以前的流行病学研究中，吸烟一直被证明与男性和女性患帕金森病的风险较低有关。基于这些观察，尼古丁被认为是一种潜在的神经保护剂。然而，吸烟和较低的帕金森病风险之间的联系可以用一个尚不清楚的第三个因素来解释，该因素增加了帕金森氏症的风险，也导致了对吸烟行为的厌恶。在这种情况下，重要的是研究来自其他来源的尼古丁，而不是香烟，是否也与帕金森病风险改变有关。由于少量尼古丁可以饱和大脑中相当大一部分尼古丁受体，因此我们能够研究饮食尼古丁摄入对帕金森病风险的潜在影响。这将提供强有力的证据，支持或反对尼古丁和改变的帕金森病风险之间的潜在偶然关系，并对开发新的预防/治疗策略也很重要。因此，我们建议进行一项大规模的前瞻性研究，以检验饮食摄入尼古丁和含有尼古丁的茄科植物是否与两个正在进行的美国队列中的帕金森病风险有关，其中包括超过78,000名从未吸烟的男性和女性。在26-32年的随访中，我们记录了自收集饮食数据以来的921例帕金森病事件。我们建议研究1)摄入更多的尼古丁和含有尼古丁的茄科植物是否与患帕金森病的风险较低相关，以及2)饮食尼古丁之间的关联是否在那些没有环境烟草烟雾暴露的人中更加明显。作为第二个目标，我们将研究尼古丁饮食摄入量和趾甲尼古丁水平之间的关系，脚趾甲尼古丁水平是1217名HPFS/NHS从不吸烟的人中尼古丁暴露的长期生物标志物，这两个数据都可用。最后，我们将探索饮食尼古丁和遗传因素(即CHRNA5、iNOS2a和SNCA)之间的可能相互作用，这些因素之前已被证明改变了吸烟与帕金森病的关系。值得注意的是，有超过900例帕金森病病例，这是唯一一项关于帕金森病危险因素的大型前瞻性调查，其中包括对饮食和其他生活方式因素的重复和详细评估。鉴于烟草中的尼古丁可能会有不良影响，饮食中尼古丁的疾病改善潜力非常有价值。由于可食用食品的安全性、可接受性和广泛的可获得性，这一结果很容易转化为临床实践。 茄科食品。

 DESCRIPTION (provided by applicant): Parkinson disease (PD) is the second most common neurodegenerative disease in the United States and affects over one million Americans; this number is growing due to population aging. Most patients eventually develop severe disability, which markedly affects their quality of life and that of their caregivers. There is thus a compellig need to develop disease modifying or neuroprotective treatments. In previous epidemiologic studies, cigarette smoking has been consistently shown to be associated with a lower risk of PD in men and women. Based on these observations, nicotine has been proposed to be a potential neuro-protective agent. However, the association between smoking and lower PD risk could be explained by a still-unknown third factor that increases the risk of PD and also causes an aversion to smoking behavior. In this context, it is of importance to examine whether nicotine from other sources, rather than cigarettes, is also associated with altered PD risk. Because a small amount of nicotine can saturate a substantial portion of nicotine receptors in the brain, we thus are able to examine the potential effects of dietary nicotine consumption on PD risk. This would provide strong evidence arguing for or against the potential casual relationship between nicotine and altered PD risk and is also important for the development of a novel prevention/treatment strategy. We thus propose to conduct a large-scale prospective study to examine whether dietary intake of nicotine and nicotine-containing solanaceae is associated with PD risk in two ongoing US cohorts including over 78,000 men and women who had never smoked. During 26-32 years of follow-up, we documented 921 incident cases of PD since dietary data were collected. We propose to examine 1) whether greater consumptions of dietary nicotine and nicotine-containing solanaceae are associated with lower risk of developing PD and 2) whether the association between dietary nicotine is more pronounced among those without environmental tobacco smoke exposure. As a secondary aim, we will examine the association between dietary intake of nicotine and toenail nicotine level, a long-term biomarker of nicotine exposure among 1,217 HPFS/NHS never-smokers with both data available. Finally, we will explore possible interactions between dietary nicotine and genetic factors (i.e., CHRNA5, iNOS2a, and SNCA) among never-smokers which have been previously shown to modify the smoking-PD relationship. Of note, with over 900 incident PD case, this is the only large prospective investigation of PD risk factors that includes repeated and detailed assessments of diet and other lifestyle factors. Given nicotine from tobacco may have adverse effects, the disease-modifying potential of dietary nicotine is of great value. This result could easily be translated in clinical practices due to the safety, acceptableness, and wide availability of edible solanaceae foods.