Novel Risk Factors For Hypertension

描述(由申请人提供)： 据估计，高血压(HTN)影响着6000万美国人，是发病率和 死亡率。饮食、循环分子以及遗传和环境之间的相互作用都可能影响发生HTN的风险。采用前瞻性研究设计(队列和嵌套病例对照研究)，我们建议在三个大的独立队列中检查突发HTN的新危险因素。 基于叶酸、其他B族维生素和蛋氨酸也会影响内皮功能的数据 通过直接或通过对循环中同型半胱氨酸的影响，我们假设较高的叶酸、维生素B6和维生素B12的摄入量将降低发生HTN的风险，而较高的蛋氨酸摄入量将增加风险。此外，我们认为循环中较高水平的HY和可溶性细胞间黏附分子-1(SICAM)增加了HTN的风险。鉴于数据显示维生素D代谢物对肾素血管紧张素系统的影响，我们还提出，较高的维生素D水平与较低的HTN风险相关。最后，我们假设MTHFR和eNOS的基因多态将显著改变叶酸和维生素B12之间的关系以及发生HTN的风险，而维生素D受体(VDR)的多态将改变维生素D水平和HTN之间的关联。这项建议的具体目的是：(1)评估新的和可改变的饮食因素与HTN事件的关系；(2)评估血浆HY、sICAM和维生素D代谢物水平与HTN后续发展的关系；(3)评估MTHFR、eNOS和VDR基因多态与影响HTN事件风险的特定环境因素之间的相互作用。这一K08奖项的候选人是约翰·P·福尔曼，医学博士，哈佛医学院医学讲师，布里格姆妇女医院肾脏科主治医师，哈佛大学公共卫生学院流行病学硕士候选人。他正在寻求在对HTN感兴趣的著名流行病学家Gary C.Curhan，M.D.，SC.D.的指导下，在高级流行病学方法方面的进一步培训和经验。该项目提案将为候选人未来的职业生涯奠定基础，成为一名独立和成功的HTN研究临床科学家。 (摘要结束)

DESCRIPTION (provided by applicant): Hypertension (HTN) affects an estimated 60 million Americans, and is a major cause of morbidity and mortality. Diet, circulating molecules, and the interaction between genetics and environment may all impact the risk of developing HTN. Using prospective study designs (cohort and nested case-control studies), we propose to examine novel risk factors for incident HTN in three large independent cohorts. Based upon data that folate, other B vitamins, and methionine can influence endothelial function either directly or through effects on circulating homocysteine (Hey), we hypothesize that higher intakes of folate, vitamin B6, and vitamin B12 will reduce the risk of incident HTN, while higher methionine intake will increase the risk. Furthermore, we propose that higher circulating levels of Hey and soluble intercellular adhesion molecule-1 (sICAM) increase the risk of HTN. Given data demonstrating effects of vitamin D metabolites on the renin angiotensin system, we also propose that higher vitamin D levels will be associated with a lower risk of HTN. Finally, we hypothesize that genetic polymorphisms in MTHFR and eNOS will significantly modify the relation between folate and vitamin B12 and the risk of incident HTN, and that polymorphisms in the vitamin D receptor (VDR) will modify the association between vitamin D levels and HTN. The specific aims of this proposal are: (1) to assess the relation between novel and modifiable dietary factors and incident HTN; (2) to assess the relation between plasma levels of Hey, sICAM, and vitamin D metabolites and the subsequent development of HTN; and (3) to assess the interaction between MTHFR, eNOS, and VDR polymorphisms and specific environmental factors as they influence the risk of incident HTN. The candidate for this K08 award is John P. Forman, M.D., an Instructor in Medicine at Harvard Medical School, attending nephrologist at Brigham and Women's Hospital, and a Masters' Candidate in Epidemiology at Harvard School of Public Health. He is seeking further training and experience in advanced epidemiologic methods under the guidance of Gary C. Curhan, M.D., Sc.D., a well-known epidemiologist with an interest in HTN. This project proposal will provide the foundation for the candidate's future career as an independent and successful clinical scientist in HTN research. (End of Abstract)