The impact of enculturation on the epigenetic relationship between chronic stress and hypertension in Yup'ik Alaska Native people

文化适应对尤皮克阿拉斯加原住民慢性应激与高血压之间表观遗传关系的影响

• 批准号: 10338067
• 负责人: BERT Brandon BOYER
• 金额: $ 69.56万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-02 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10338067
• 关键词: Acculturation; Address; Adherence; Alaska Native; Alcohol consumption; American Indians; Animals; Behavior; Behavioral; Belief; Biological; Biological Aging; Biological Process; Blood Pressure; Buffers; C-reactive protein; Cardiovascular Diseases; Chronic; Chronic stress; DNA Methylation; Data Reporting; Development; Disease; Epigenetic Process; Ethnic group; Event; Exercise; Exhibits; Functional disorder; Gene Expression; Glucocorticoids; Glycosylated hemoglobin A; Goals; Health; Health Promotion; Health behavior; High Density Lipoprotein Cholesterol; Human; Hydrocortisone; Hyperphagia; Hypertension; Indigenous; Individual; Inflammation; Interleukin-6; Ischemic Stroke; LDL Cholesterol Lipoproteins; Lead; Length; Leukocytes; Life Style; Link; Lipids; Maintenance; Mediating; Metabolic dysfunction; Methylation; Minority Groups; Mitochondria; Modeling; Modification; Molecular; Native-Born; Not Hispanic or Latino; Obesity; Organ; Outcome Measure; Outcome Study; Participant; Patient Self-Report; Persons; Plasma; Population; Prevalence; Psychological Stress; Reporting; Research; Risk; Risk Factors; Role; Salivary; Site; Smoking; Source; Stress; Stressful Event; Stroke; Telomere Shortening; Testing; Tobacco use; Trauma; Triglycerides; Yup' ik; allostatic load; base; blood pressure regulation; coping; cultural values; disorder risk; effective intervention; environmental stressor; epigenome; fasting plasma glucose; genome wide methylation; health disparity; improved; insight; maladaptive behavior; methylation pattern; poor sleep; premature; prevent; protective effect; racial and ethnic; resilience; response; social factors; social health determinants; social stressor; socioeconomics; stress resilience; stressor; stroke incidence; stroke risk; telomere

Project Summary The objective of the proposed research is to identify molecular mechanisms linking the protective role of culture to blood pressure regulation, a major risk factor for stroke in Yup'ik Alaska Native people. The prevalence of stroke is higher among American Indian and Alaska Native (AIAN) populations than in any other U.S. racial/ethnic group. Chronic psychological stress increases the risk for hypertension, and is the most frequently cited stroke risk factor in AIAN populations. The prevalence of stroke has increased over the past 25 years, and is likely brought on by chronic stressors including historical trauma, cultural change and adverse socioeconomic conditions which, in turn, increases the likelihood of unhealthy behavioral coping responses (e.g., smoking, reduced exercise, poor sleep and overeating). However, our previous research has shown that both strong adherence to Yup'ik cultural traditions (enculturation) and dual adherence to Yup'ik and White culture (biculturalism) are associated with healthier blood pressure when compared to Yup'ik individuals adhering to a more Western lifestyle (acculturation). No previous research has identified the molecular events underlying the basis for the protective effects of enculturation/biculturalism-induced resilience (EBIR) on risk for hypertension, representing a critical barrier to the development of culturally effective interventions aimed at promoting health. The proposed research examines the role of EBIR at each step of the stress-disease cascade – a model based on extensive research linking chronic stressful events to biological mechanisms and diseases such as hypertension. We hypothesize that EBIR blocks or buffers adverse individual and environmental stressors resulting in reduced metabolic dysfunction and inflammation, inhibition of epigenetic dysregulation, and maintenance of leukocyte telomere length, all or some of which lead to healthy blood pressure. We test these hypotheses by addressing the following Specific Aims (SAs): SA1 - Conduct latent class analysis using self- reported data about enculturation, biculturalism, and chronic stress from 800 Yup'ik participants to form classes based on their degree of EBIR/stress (SA1a), followed by evaluating the relationship between EBIR/stress latent classes and maladaptive health-related behaviors as well as between blood pressure, the main study outcome measure (SA1b); SA2 - Evaluate the association between EBIR/stress latent classes with metabolic dysfunction (salivary cortisol, fasting plasma glucose and HbA1c levels, and lipid levels), mitochondrial allostatic load, and chronic low-grade inflammation; and SA3 - Determine the impact of EBIR/stress latent classes on epigenome- wide DNA methylation and downstream changes in gene expression (SA3a) as well as quantify the association between methylation sites and blood pressure (SA3b), and test whether differential methylation mediates the association between EBIR/stress latent classes and blood pressure (SA3c). We will also evaluate leukocyte telomere length among individuals in each of the EBIR/stress latent classes (SA3d) in order to determine whether EBIR reduces the impact of chronic stress on premature telomere shortening, an indicator of biological aging.

项目摘要 拟议的研究的目的是确定与培养作用联系起来的分子机制 对于血压调节，是阿拉斯加Yup'ik Alaska中风的主要危险因素。流行率 美国印第安人和阿拉斯加本地人（Aian）人口中的中风高于其他任何美国种族/种族 团体。慢性心理压力增加了高血压的风险，是最常见的中风 艾安人口的危险因素。过去25年中，中风的患病率有所增加，很可能 由慢性压力源购买，包括历史创伤，文化变革和广告社会经济 反过来增加行为应对反应的可能性（例如，吸烟， 减少运动，睡眠不佳和暴饮暴食）。但是，我们以前的研究表明，两者都很强 遵守Yup'ik文化传统（文化）和双重遵守Yup'ik和白人文化 （双文化主义）与遵守A的Yup'ik个体相比，血压更健康 更多西方生活方式（适应）。以前没有研究确定 培养/双文化诱导的韧性（EBIR）对高血压风险的受保护作用的基础 代表了旨在促进健康的文化有效干预措施发展的关键障碍。 拟议的研究考试EBIR在压力 - 疾病级联的每个步骤中的作用 - 一个基于模型的 在广泛的研究中，将慢性压力事件与生物学机制和疾病（例如 高血压。我们假设Ebir阻滞或缓冲区不利的个体和环境压力源 导致代谢功能障碍和注射降低，表观遗传失调的抑制作用和 维持白细胞端粒长度，全部或某些导致健康的血压。我们测试这些 通过解决以下特定目标（SAS）：SA1-使用自我进行潜在类别分析来假设 报告了800名参与者的培养，双文化主义和慢性压力的数据 根据它们的EBIR/压力程度（SA1A），然后评估eBir/压力潜在的关系 阶级和适应不良的健康相关行为以及血压之间的主要研究结果 测量（SA1B）; SA2-评估EBIR/压力潜在类别与代谢功能障碍之间的关联 （唾液皮质醇，禁食等离子体葡萄糖和HBA1C水平以及脂质水平），线粒体同骨负荷和 慢性低度炎症；和SA3-确定Ebir/压力潜在类别对表观基因组的影响 宽DNA甲基化和基因表达（SA3A）的下游变化，并量化关联 在甲基化部位和血压（SA3B）之间，并测试差甲基化是否介导 EBIR/压力潜在类别与血压（SA3C）之间的关联。我们还将评估白细胞 每个eBIR/压力潜在类别（SA3D）中个体之间的端粒长度，以确定是否是否 埃比尔（Ebir）减少了慢性应激对生物衰老的指标过早端粒缩短的影响。