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

描述（由申请人提供）：候选人，Honglei Chen，医学博士，博士，在帕金森氏症（PD）方面有两年多的研究经验，目前是哈佛公共卫生学院的研究助理。陈博士的研究兴趣包括散发性PD和其他神经退行性疾病的环境和遗传病因学，他计划在这一领域发展独立的学术生涯。在这份K 08提案中，Chen博士提出在癌症预防研究-II营养队列（CPS-IIn）中对饮食和散发性PD风险进行大型前瞻性研究，并在卫生专业人员随访研究（HPFS）和护士健康研究（NHS）中对PD与遗传多态性和基因-饮食相互作用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PD与饮食摄入量的关系，重点是叶酸，咖啡，膳食抗氧化剂，脂肪，酒精和乳制品。CPS-IIn中PD事件的确认正在进行中，他们预计将在1992年至2001年期间诊断出550例明确和可能的PD病例。在HPFS和NHS队列中，他将评价PD风险与NAT 2、CYP 1A 2、ADH 2、ADH 3、ADH 4和MTHFR常见多态性的相关性。他还将首次探索PD病因中的基因-饮食相互作用，包括NAT 2，CYP 1A 2和咖啡因摄入; ADH 2，ADH 3，ADH 4和酒精摄入; MTHFR和叶酸摄入。到2000年，他们记录了567例确诊和可能的PD病例，其中454例提供了血液或脸颊细胞进行遗传分析。在这项拟定的巢式病例对照研究中，将为每个年龄和性别匹配的PD病例选择两个对照。本提案中包括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）和有效的饮食评估以及严格的结局确定。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，K 08基金将同时实现两个重要目标：帮助陈博士发展成为神经系统疾病流行病学独立研究人员的技能，并进一步加深我们对饮食，基因和PD病因之间复杂相互关系的理解。

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.