The Psychosocial & Genetic Basis of Estrogen Metabolism & Blood Pressure in Aging

社会心理

• 批准号: 7479583
• 负责人: CHRISTOPHER MAURICE MASI
• 金额: $ 11.91万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479583
• 关键词: 17p; Acute; Address; Adult; Affect; Age; Aging; Alcohol consumption; Anger; Animals; Antihypertensive Agents; Behavioral; Behavioral Genetics; Biological Markers; Biology; Black race; Blood; Blood Pressure; Blood Vessels; COMT gene; CYP1B1 gene; CYP3A4 gene; Cardiovascular Diseases; Cardiovascular system; Catechol O-Methyltransferase; Catecholamines; Characteristics; Chicago; Chronic; Cohort Studies; Coronary Arteriosclerosis; Coronary heart disease; Data; Demographic Aging; Dietary Sodium; Disease; Education; Elderly; Endocrinology; Ensure; Enzymes; Estradiol; Estrogen Metabolism; Estrogens; Ethnic Origin; Exercise; Family history of; Framingham Heart Study; Funding; Gender; Gene Expression; Genes; Genetic; Genetic Determinism; Genetic Predisposition to Disease; Geriatric Psychiatry; Glucocorticoids; Goals; Health; Hormones; Hostility; Human; Hypertension; Hypertension induced by pregnancy; Incidence; Individual; Inherited; Intake; Life; Link; Loneliness; Low income; Marital Status; Mediator of activation protein; Menopausal Status; Menopause; Mental Depression; Mentorship; Mineralocorticoids; Modeling; Myocardial Infarction; Netherlands; Nucleotides; Numbers; Obesity; Outcome; Pathway interactions; Pattern; Pharmaceutical Preparations; Population; Postmenopause; Prevalence; Production; Psychological Stress; Psychosocial Factor; Race; Range; Registries; Research; Research Personnel; Risk; Risk Factors; Sampling; Serum; Single Nucleotide Polymorphism; Smoking; Stress; Stroke; Supplementation; Syndrome; Tobacco use; Training; Twin Multiple Birth; Urine; Vasodilation; Woman; Women' s Health; age related; base; cardiovascular disorder risk; cohort; design; diet and exercise; dietary excess; disability; heart disease risk; men; middle age; older men; pressure; programs; psychologic; psychosocial; response; social; urinary; young adult

DESCRIPTION (provided by applicant): Despite the declining prevalence of chronic disability among older individuals, age continues to be associated with risk of hypertension and hypertension-related diseases, including coronary artery disease and stroke. In this K08 application, the PI will aggressively explore the mechanisms underlying age-related hypertensive disease, especially among those at highest risk. The theoretical underpinnings of the proposed research are based upon data generated by the PI within the Chicago Health, Aging, and Social Relations Study (CHASRS). Funded by the NIA and directed by Dr. John Cacioppo, this study seeks to explain the effect of psychosocial factors, including loneliness, on age-related changes in systolic blood pressure (SBP). Recent data from CHASRS indicate that loneliness and hostility are associated with urinary estrogen metabolite concentrations and these concentrations are associated with SBP. Because diet, exercise, and stress hormones can influence estrogen metabolism, it is hypothesized that many risk factors for hypertension are associated with estrogen metabolism and that serum levels of estrogen metabolites are associated with SBP. The specific aims are designed to explore these hypotheses in the CHASRS cohort and validate them in a larger cohort from the Netherlands Twin Registry. Specific Aim 1 is to determine which serum estrogen metabolite or combination of serum estrogen metabolites best predicts systolic blood pressure in middle aged and older men and women. Specific Aim 2 is to determine the degree to which serum estrogen metabolite concentrations are correlated with urinary estrogen metabolite concentrations. Specific Aim 3 is to determine whether single nucleotide polymorphisms (SNP's) of genes which encode specific estrogen metabolizing enzymes predict the serum concentrations of the estrogen metabolites most closely associated with systolic blood pressure. Specific Aim 4 is to determine the extent to which estrogen metabolites explain the associations between established hypertension risk factors and systolic blood pressure in middle aged and older men and women. Completion of these aims, as well as mentorship by Dr. Cacioppo and additional training in psychology, geriatrics, endocrinology, vascular biology, and genetics, will ensure the PI develops into an independent clinician investigator with expertise in the demographic, psychosocial, and genetic determinants of estrogen metabolism and age-related blood pressure changes.

描述（由申请人提供）：尽管老年人慢性残疾的患病率下降，但年龄仍然与高血压和高血压相关疾病（包括冠状动脉疾病和中风）的风险相关。在本K08申请中，PI将积极探索年龄相关性高血压疾病的潜在机制，尤其是在高风险人群中。拟议研究的理论基础是基于芝加哥健康、老龄化和社会关系研究（CHASRS）中PI生成的数据。由NIA资助并由John Cacioppo博士指导的这项研究旨在解释包括孤独在内的心理社会因素对收缩压（SBP）年龄相关变化的影响。CHASRS的最新数据表明，孤独和敌意与尿雌激素代谢产物浓度相关，这些浓度与SBP相关。由于饮食、运动和应激激素可以影响雌激素代谢，因此假设许多高血压的危险因素与雌激素代谢相关，血清雌激素代谢产物水平与SBP相关。具体目标是在CHASRS队列中探索这些假设，并在荷兰双胞胎登记处的更大队列中验证它们。具体目标1是确定哪种血清雌激素代谢物或血清雌激素代谢物的组合最能预测中老年男性和女性的收缩压。具体目标2是确定血清雌激素代谢物浓度与尿雌激素代谢物浓度的相关程度。具体目标3是确定编码特定雌激素代谢酶的基因的单核苷酸多态性（SNP）是否预测与收缩压最密切相关的雌激素代谢物的血清浓度。具体目标4是确定雌激素代谢产物在多大程度上解释了已确定的高血压危险因素与中老年男性和女性收缩压之间的关联。这些目标的完成，以及Cacioppo博士的指导和心理学，老年病学，内分泌学，血管生物学和遗传学的额外培训，将确保PI发展成为一名独立的临床研究者，具有人口统计学，心理社会学和雌激素代谢和年龄相关血压变化的遗传决定因素的专业知识。