Diet, gene-diet interactions and risk of Parkinson's

描述（申请人提供）： 候选人陈红雷，医学博士、哲学博士，拥有两年以上帕金森病（PD）研究经验，现为哈佛大学公共卫生学院研究员。陈博士的研究兴趣包括散发性帕金森病和其他神经退行性疾病的环境和遗传病因学，他计划在该领域发展独立的学术生涯。在这项 K08 提案中，陈博士提议在癌症预防研究-ll 营养队列 (CPS-IIn) 中对饮食和散发性帕金森病风险进行大型前瞻性调查，并在卫生专业人员随访研究 (HPFS) 和护士健康研究 (NHS) 中对遗传多态性和基因-饮食相互作用的帕金森病进行大型巢式病例对照研究。在 CPS-IIn 中，他将前瞻性地研究 162,408 名美国男性和女性的 PD 与饮食摄入量的关系，重点关注叶酸、咖啡、膳食抗氧化剂、脂肪、酒精和乳制品。 CPS-IIn 中的 PD 病例确认工作正在进行中，他们预计将记录 1992 年至 2001 年间诊断出的 550 例明确和可能的 PD 病例。在 HPFS 和 NHS 队列中，他将评估 PD 风险与 NAT2、CYP1A2、ADH2、ADH3、ADH4 和 MTHFR 常见多态性的关联。他还将首次探索 PD 病因中基因与饮食的相互作用，包括 NAT2、CYP1A2 和咖啡因摄入量； ADH2、ADH3、ADH4 和酒精摄入量； MTHFR 和叶酸摄入量。 2000 年，他们记录了 567 例明确的和可能的帕金森病病例，其中 454 例提供了血液或颊细胞用于遗传分析。在这项拟议的巢式病例对照研究中，将为每个 PD 病例选择两个对照，以匹配年龄和性别。该提案中包含的所有三个队列都是成熟的大型前瞻性队列，具有全面（基线和更新）和经过验证的饮食评估和严格的结果确定。此外，这项研究的范围使其成为迄今为止最大的调查之一。已完成或接近完成的数据收集将进一步使本研究最具成本效益。因此，这笔K08资助将同时实现两个重要目标：帮助陈博士培养成为神经系统疾病流行病学独立研究员的技能，并进一步了解饮食、基因和帕金森病病因学之间复杂的相互关系。

DESCRIPTION (provided by applicant): The candidate, Honglei Chen, M.D., Ph.D., has more than two years research experience in Parkinson's disease (PD) and is currently a Research Associate at Harvard School of Public Health. Dr. Chen's research interest includes the environmental and genetic etiology of sporadic PD and that of other neurodegenerative diseases, and he plans to develop an independent academic career in this area. In this K08 proposal, Dr. Chen proposes a large prospective investigation of diet and risk of sporadic PD in the Cancer Prevention Study-ll Nutrition Cohort (CPS-IIn) and a large nested case-control study of PD with genetic polymorphisms and gene-diet interactions in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). In the CPS-IIn, he will prospectively examine among 162,408 US men and women associations of PD with dietary intakes, focusing on folate, coffee, dietary antioxidants, fat, alcohol, and dairy products. Confirmation of incident PD cases in CPS-IIn is ongoing and they expect to document 550 definite and probable PD cases diagnosed between 1992 and 2001. In the HPFS and NHS cohorts, he will evaluate the associations of PD risk with common polymorphisms of NAT2, CYP1A2, ADH2, ADH3, ADH4, and MTHFR. He also will, for the first time, explore gene-diet interactions in PD etiology, including NAT2, CYP1A2 and caffeine intake; ADH2, ADH3, ADH4, and alcohol intake; and MTHFR and folate intake. Through the year of 2000, they have documented 567 definite and probable PD cases and 454 of them provided either blood or cheek cells for genetic analysis. In this proposed nested case-control study, two controls will be selected for each PD case matching on age and gender. All three cohorts included in this proposal are well-established large prospective cohorts with comprehensive (baseline and updated) and validated dietary assessments and rigorous outcome ascertainments. Moreover, the scope of this study makes it one of the largest investigations to date. The completed or nearly completed data collection will further make this study most cost-effective. Therefore, this K08 grant will simultaneously accomplish two important goals: helping Dr. Chen develop the skills to become an independent researcher in the epidemiology of neurological diseases and furthering our understanding of the complex interrelationships among diet, genes and PD etiology.