Vitamin D Status, Vitamin D Receptor Gene Variants, and Hypertension Risk

维生素 D 状况、维生素 D 受体基因变异和高血压风险

• 批准号: 8130777
• 负责人: Lu Wang
• 金额: $ 8.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-20 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8130777
• 关键词: Address; Aldosterone; Award; Binding; Biochemical Genetics; Biochemical Markers; Biological; Biological Markers; Blood Pressure; Candidate Disease Gene; Cardiovascular Diseases; Cessation of life; Chronic Disease; Collaborations; Data; Databases; Development; Epidemiologic Studies; Epidemiologist; Epidemiology; Evaluation; Fostering; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Haplotypes; Health; Health Professional; High Prevalence; Hypertension; Hypotension; Intervention; Investigation; Knowledge; Link; Mentors; Metabolism; Mixed Function Oxygenases; Nested Case-Control Study; Nutritional; Outcome; Pathway interactions; Phase; Physicians; Plasma; Population; Prevalence; Primary Prevention; Prospective Studies; Public Health; RXR; RXRA gene; RXRB gene; RXRG gene; Receptor Gene; Recommendation; Renin-Angiotensin-Aldosterone System; Research; Research Activity; Research Personnel; Research Project Grants; Research Training; Resources; Risk; Role; Signal Pathway; Solid; Testing; Training; Training and Education; Variant; Vitamin D; Vitamin D-Binding Protein; Vitamin D2; Vitamin D3 Receptor; Woman; Women' s Health; base; career development; cohort; design; follow-up; genetic association; genetic epidemiology; genetic variant; genome wide association study; high risk; hypertension prevention; improved; male; men; normotensive; novel strategies; nutrition; nutritional epidemiology; prevent; programs; prospective; public health relevance; randomized trial; research facility; research study; skills

DESCRIPTION (provided by applicant): The goal of this K99/R00 proposal is to build a mentored and independent research program for the applicant to comprehensively investigate the nutritional, biochemical, and genetic basis for vitamin D in the development of hypertension in women and men. Finding novel strategies to prevent hypertension, the most prevalent chronic disease in the U.S., is of critical public health importance. Accumulating evidence suggest that vitamin D is a promising nutritional agent for hypertension prevention. However, epidemiologic studies of vitamin D in relation to hypertension remain limited. Few prospective studies have examined the association between baseline circulating 25(OH)-vitamin D (25(OH)D), the biochemical marker of vitamin D status, and the subsequent risk of developing hypertension. Genetic epidemiologic studies to date have only tested a few polymorphisms in the vitamin D receptor (VDR) gene, among many genes in the vitamin D pathway, for association with blood pressure (BP) or hypertension. Moreover, the potential interaction of circulating vitamin D and vitamin D pathway gene polymorphisms on the risk of hypertension is largely unexplored. We will therefore investigate these associations in two large prospective cohorts: the Women's Health Study and the Physicians' Health Study. The applicant of this award has solid education and training background in cardiovascular disease (CVD) epidemiology and has access to rich research, facilities, and collaboration resources. The current goal of the applicant is to advance her knowledge and skills in genetic epidemiology research. Her long-term goal is to become an independent epidemiologist that investigates the biochemical and genetic markers relevant to the metabolism and functionality of nutritional factors in the development of hypertension and other CVD-related outcomes. During the K99 phase, the applicant will receive focused training in genetic epidemiology through didactic coursework, mentored research, seminars participation, and skill practice. The applicant will also conduct initial analyses of plasma 25(OH)D and genetic variants in vitamin D pathway (candidate genes including VDR, CYP27B1, CYP24A1, GC, RXRA, RXRB, and RXRG) in relation to BP and hypertension. During the R00 phase, the applicant will further extend her research to two specifically designed nested case-control studies of hypertension, assess prospective association between baseline plasma 25(OH)D and subsequent risk of hypertension, investigate the underlying mechanisms, as well as explore the potential gene-biomarker interactions. Findings from this study will substantially improve our understanding on the role of vitamin D in the development of hypertension and help optimize intervention strategy for hypertension prevention. Meanwhile the focused training and research together will offer the applicant a unique opportunity to integrate genetic epidemiology with her current research in CVD and nutritional epidemiology and greatly foster her career development to become an independent investigator on nutrition, metabolism, and genetics in the development of hypertension and CVD. PUBLIC HEALTH RELEVANCE: The proposed research project will substantially improve our understanding regarding the role of vitamin D in the development of hypertension, help identify high risk population and optimize intervention strategy, and provide basis for public health recommendations on the optimal vitamin D status for primary prevention of hypertension and other cardiovascular disease-related outcomes.

描述（由申请人提供）：本 K99/R00 提案的目标是为申请人建立一个受指导的独立研究计划，以全面研究维生素 D 在女性和男性高血压发展中的营养、生化和遗传基础。寻找新的策略来预防高血压（美国最常见的慢性疾病）对于公共卫生至关重要。越来越多的证据表明维生素 D 是一种有前景的预防高血压的营养剂。然而，维生素 D 与高血压相关的流行病学研究仍然有限。很少有前瞻性研究探讨了基线循环 25(OH)-维生素 D (25(OH)D)（维生素 D 状态的生化标志物）与随后发生高血压的风险之间的关联。迄今为止，遗传流行病学研究仅测试了维生素 D 通路中的许多基因中维生素 D 受体 (VDR) 基因的少数多态性与血压 (BP) 或高血压的关系。此外，循环维生素 D 和维生素 D 通路基因多态性与高血压风险之间的潜在相互作用在很大程度上尚未被探索。因此，我们将在两个大型前瞻性队列中研究这些关联：女性健康研究和医生健康研究。该奖项的申请人在心血管疾病（CVD）流行病学方面拥有扎实的教育和培训背景，并可以获得丰富的研究、设施和合作资源。申请人当前的目标是提高她在遗传流行病学研究方面的知识和技能。她的长期目标是成为一名独立的流行病学家，研究与高血压和其他心血管疾病相关结果的发展中营养因素的代谢和功能相关的生化和遗传标记。在 K99 阶段，申请人将通过教学课程、指导研究、研讨会参与和技能实践接受遗传流行病学方面的重点培训。申请人还将对血浆25(OH)D和维生素D途径中的遗传变异（候选基因包括VDR、CYP27B1、CYP24A1、GC、RXRA、RXRB和RXRG）与血压和高血压的关系进行初步分析。在R00阶段，申请人将进一步将其研究扩展到两项专门设计的高血压巢式病例对照研究，评估基线血浆25(OH)D与随后的高血压风险之间的前瞻性关联，研究潜在机制，并探索潜在的基因-生物标志物相互作用。这项研究的结果将大大提高我们对维生素 D 在高血压发生中的作用的认识，并有助于优化高血压预防的干预策略。同时，集中的培训和研究将为申请人提供独特的机会，将遗传流行病学与她目前在心血管疾病和营养流行病学方面的研究相结合，并极大地促进她的职业发展，成为高血压和心血管疾病发展中营养、代谢和遗传学的独立研究者。 公共卫生相关性：拟议的研究项目将大大提高我们对维生素 D 在高血压发展中的作用的理解，帮助识别高危人群并优化干预策略，并为关于高血压和其他心血管疾病相关结果的一级预防的最佳维生素 D 状态的公共卫生建议提供基础。

项目成果

Calcium intake and risk of cardiovascular disease: a review of prospective studies and randomized clinical trials.

• DOI: 10.2165/11595400-000000000-00000
• 发表时间: 2012-04-01
• 期刊: American journal of cardiovascular drugs : drugs, devices, and other interventions
• 作者: Wang L;Manson JE;Sesso HD
• 通讯作者: Sesso HD