Novel Risk Factors For Hypertension

描述（由申请人提供）： 高血压（HTN）影响估计6000万美国人，并且是发病率和死亡率的主要原因。 mortality.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HTN的风险。使用前瞻性研究设计（队列和巢式病例对照研究），我们建议在三个大型独立队列中检查HTN事件的新风险因素。 根据叶酸、其他B族维生素和甲硫氨酸可以影响内皮功能的数据 直接或通过对循环同型半胱氨酸（Hey）的影响，我们假设叶酸，维生素B6和维生素B12的摄入量增加将降低HTN事件的风险，而蛋氨酸摄入量增加将增加风险。此外，我们认为，高水平的循环中的嘿和可溶性细胞间粘附分子-1（sICAM）增加HTN的风险。鉴于数据表明维生素D代谢产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水平将与HTN的风险较低相关。最后，我们假设MTHFR和eNOS的遗传多态性将显著改变叶酸和维生素B12与HTN发病风险之间的关系，维生素D受体（VDR）的多态性将改变维生素D水平与HTN之间的关联。该提案的具体目的是：（1）评估新型和可改变的饮食因素与HTN事件之间的关系;（2）评估血浆Hey、sICAM和维生素D代谢物水平与随后HTN发展之间的关系;（3）评估MTHFR、eNOS和VDR多态性与特定环境因素之间的相互作用，因为它们影响HTN事件的风险。这个K 08奖的候选人是约翰·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病科主治医师，哈佛公共卫生学院流行病学硕士候选人。他正在加里C的指导下寻求先进流行病学方法的进一步培训和经验。Curhan，医学博士，科学博士，一位对高血压感兴趣的著名流行病学家该项目提案将为候选人未来作为HTN研究中独立和成功的临床科学家的职业生涯奠定基础。 (End摘要）

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)