Social Immunoepigenetic Conditioning of Diabetes Disparities

糖尿病差异的社会免疫表观遗传调节

• 批准号: 10268258
• 负责人: Alika Keolaokalani Maunakea
• 金额: $ 88.64万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2022-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268258
• 关键词: 19 year old; 2019-nCoV; Abate; Address; Affect; Age; Behavior; Behavioral; Biological; Biometry; Businesses; COVID-19; COVID-19 disparity; COVID-19 testing; Cardiometabolic Disease; Cardiovascular Diseases; Caring; Cells; Child; Chronic; Clinic; Clinical; Cohort Studies; Collaborations; Communities; Community Health Education; Community Healthcare; Community Networks; Conflict (Psychology); Country; Coupled; DNA; DNA Methylation; Data; Data Collection; Diabetes Mellitus; Discrimination; Education; Educational Curriculum; Epigenetic Process; Ethnic group; Etiology; Evaluation; Exposure to; FDA approved; Family; Filipino; Foundations; Frequencies; Fright; Funding; Gene Expression; Genes; Genetic; Genetic Transcription; Global Change; Goals; Grant; Growth; Hawaii; Health; Health Personnel; Health Professional; Health Status; Health behavior; Healthcare; High Prevalence; Hotlines; Household; Housing; Immune; Immune system; Immunologics; Individual; Infection; Inflammation; Inflammatory; Insulin Resistance; Job loss; K-12 Education; Knowledge; Language; Lead; Mediating; Mission; Modeling; Molecular Diagnostic Testing; Native Hawaiian; Neighborhood Health Center; Neighborhoods; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Pacific Island Americans; Parents; Patients; Perception; Physical activity; Physicians; Physiological; Play; Population; Population Heterogeneity; Poverty; Prospective Studies; Protocols documentation; Public Health; Public Health Education; RADx Underserved Populations; Race; Recording of previous events; Research; Research Personnel; Role; Rural; Rural Community; Safety; School-Age Population; Schools; Science; Services; Shapes; Site; Social Environment; Students; Technology; Testing; Time; Vaccines; Viral; Vulnerable Populations; Work; Youth; base; cardiometabolic risk; cardiometabolism; cardiovascular disorder risk; clinical Diagnosis; clinical predictors; community center; community engagement; conditioning; design; disadvantaged population; disease diagnosis; disorder risk; early onset; epigenomics; ethnic disparity; ethnic diversity; experience; follow-up; gene environment interaction; genome-wide; glycemic control; health care availability; health disparity; high risk population; improved; infection rate; innovation; insight; member; methylomics; monocyte; mortality; multi-ethnic; multidisciplinary; novel; nutrition; outreach; outreach program; pandemic disease; patient oriented; population based; predictive signature; preservation; racial and ethnic; remote communities; reproductive; resilience; response; social; social factors; socioeconomics; systemic inflammatory response; testing access; testing uptake; underserved community; uptake

Native Hawaiians and Pacific Islanders (NHs/PIs) experience a disproportionately higher prevalence and earlier onset of cardiometabolic health outcomes, including Type-2 diabetes mellitus (DM) and cardiovascular disease (CVD), than other racial/ethnic groups. These health disparities may result from the social environment shaping an individual’s health behaviors (e.g. nutrition, physical activity, and education) and physiological responses that may mediate gene-environment interactions. The detrimental effects of social environments may include an increase in systemic inflammation, a hallmark of cardiometabolic diseases where monocytes of the immune system play a major role. We observed neighborhood social environments that associated with inflammation in vulnerable populations. Additionally, other studies show that monocyte-mediated inflammation leads to insulin resistance in target cells and heightened risk of cardiometabolic diseases. Epigenetic mechanisms, including DNA methylation, regulate transcription of pro-inflammatory genes in monocytes. We posit that neighborhood social environment leads to global changes in DNA methylation states in immune cells associated with cardiometabolic disease risk. In our work, we observed significant genome-wide changes to DNA methylation and gene expression states of pro-inflammatory genes that associated with monocyte inflammatory activity and glycemic control in DM patients, and a robust DNA methylomic signature of insulin resistance in monocytes that correlated with CVD risk. Together, these data suggest that cardiometabolic diseases may in part result from social environment-induced changes to the epigenomic landscape in monocytes underlying their inflammatory states. In this study, we will address whether the neighborhood social environment impacts epigenomic variability in monocytes across different ethnic populations in Hawaii and account for cardiometabolic health disparities, specifically to that of DM in NHs/PIs. To do so, we propose to integrate detailed individual-level health behavior, clinical/immunologic, genetic, and monocyte-specific epigenomic data with neighborhood-level social environment data from our Multiethnic Cohort Study (MEC). By using a population-based prospective study with viably preserved cells, we will have an unprecedented opportunity to examine the translational utility of epigenomic information in predicting clinically diagnosed DM that occurred during a 20-year follow-up. As NHs/PIs have disproportionately high rates of DM, we anticipate an increased frequency of an immunoepigenetic signature predictive of DM outcomes, which would provide novel insight into the etiology of health disparities. Therefore, we believe our social epigenomic multiethnic study meets the overall goals of this FOA to advance the science of epigenomics focused on health disparities, expand approaches for understanding epigenetic mechanisms by which social factors lead to biological changes that affect health disparities, and promote epigenetics research to better diagnose disease risk or resiliency among disadvantaged populations.

夏威夷原住民和太平洋岛民（NHS/PIS）的患病率不成比例 心脏代谢健康结果的早期发作，包括2型糖尿病（DM）和 与其他种族/族裔相比，心血管疾病（CVD）。这些健康差异可能是由 社会环境塑造个人的健康行为（例如营养，体育锻炼和教育）和 可能介导基因环境相互作用的身体反应。社会的不利影响 环境可能包括增加全身感染，这是心脏代谢性疾病的标志 免疫系统的单核细胞起主要作用。我们观察到邻里社会环境 与弱势群体的炎症有关。此外，其他研究表明单核细胞介导 炎症会导致靶细胞胰岛素抵抗，并增加心脏代谢的风险 疾病。表观遗传机制，包括DNA甲基化，调节促炎的转录 单核细胞中的基因。我们认为社区社会环境会导致全球DNA变化 与心脏代谢疾病风险相关的免疫细胞中的甲基化态。在我们的工作中，我们观察到 全基因组对DNA甲基化和促炎基因的基因表达状态的显着变化 DM患者中与单核细胞炎症活性和血糖控制相关的，以及强大的DNA 与CVD风险相关的单核细胞中胰岛素耐药性的甲基组学特征。在一起，这些数据 表明心脏代谢性疾病可能部分是由于社会环境引起的变化而引起的 单核细胞中其炎症状态下的表观基因组景观。在这项研究中，我们将解决 邻里社会环境是否影响不同不同的单核细胞的表观基因组变异性 夏威夷的族裔人口，并说明心脏代谢的健康分配，特别是DM NHS/PIS。为此，我们建议整合详细的个人级健康行为，临床/免疫学， 来自我们的遗传和单核细胞特异性表观基因组数据。 多民族队列研究（MEC）。通过使用具有过度保存细胞的基于人群的前瞻性研究，我们 将有前所未有的机会检查表观基因组信息的转化效用 预测在20年随访中发生的临床诊断DM。如NHS/PI所具有的 DM的高度不成比例，我们预计免疫概念签名的频率会增加 预测DM结果，这将为健康差异的病因提供新的见解。所以， 我们认为，我们的社会表观基因组学多民族研究符合该FOA的总体目标，以提高科学 表观基因组学的重点是健康分布，扩展了理解表观基因组机制的方法 社会因素导致生物学变化影响健康差异，并促进表观遗传学 研究以更好地诊断疾病人群中的疾病风险或韧性。