Social Immunoepigenetic Conditioning of Diabetes Disparities

糖尿病差异的社会免疫表观遗传调节

基本信息

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
项目类别：
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

项目摘要

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/PI) 的患病率异常高以及更早发生心脏代谢健康结果，包括 2 型糖尿病 (DM) 和心血管疾病（CVD）高于其他种族/族裔群体，这些健康差异可能是由于塑造个人健康行为的社会环境（例如营养、体育活动和教育）以及可能介导基因-环境相互作用的生理反应。环境可能包括全身炎症的增加，这是心脏代谢疾病的一个标志，其中我们观察到，免疫系统的单核细胞发挥着重要作用。此外，其他研究表明，单核细胞介导的炎症与易感人群的炎症有关。炎症导致靶细胞胰岛素抵抗和牙髓瘤心脏代谢风险表观遗传机制，包括 DNA 甲基化，调节促炎症的转录。我们假设邻近的社会环境会导致 DNA 的整体变化。在我们的工作中，我们观察到与心脏代谢疾病风险相关的免疫细胞的甲基化状态。 DNA甲基化和促炎基因的基因表达状态发生显着的全基因组变化与 DM 患者的单核细胞炎症活动和血糖控制相关，以及强大的 DNA 与 CVD 风险相关的单核细胞胰岛素抵抗的甲基组学特征。表明心脏代谢疾病可能部分是由于社会环境引起的在这项研究中，我们将探讨单核细胞炎症状态下的表观基因组景观。邻里社会环境是否影响不同地区单核细胞的表观基因组变异夏威夷的种族人口并解释了心脏代谢健康差异，特别是糖尿病的差异为此，我们建议整合详细的个人层面的健康行为、临床/免疫学、遗传和单核细胞特异性表观基因组数据以及来自我们的社区级社会环境数据多种族队列研究 (MEC) 通过使用基于人群的前瞻性研究，对存活的细胞进行研究。将有一个前所未有的机会来检验表观基因组信息的转化效用预测 20 年随访期间发生的临床诊断 DM。 DM 发病率不成比例地高，我们预计免疫表观遗传特征的频率会增加预测 DM 的结果，这将为了解健康差异的病因学提供新的见解。我们相信我们的社会表观基因组多种族研究符合 FOA 的总体目标，以推动科学发展表观基因组学的重点是健康差异，扩展了理解表观遗传机制的方法社会因素导致影响健康差异并促进表观遗传学的生物变化研究以更好地诊断弱势群体的疾病风险或恢复能力。