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Socioecological Determinants of Immunoepigenetic Signatures of Diabetes Risk in Indigenous Communities

原住民社区糖尿病风险免疫表观遗传特征的社会生态决定因素

基本信息

批准号：
10458062
负责人：
Alika Keolaokalani Maunakea
金额：
$ 66.75万
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：
2021
资助国家：
美国
起止时间：
2021-07-28 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10458062
关键词：
Address Adult Affect Age Behavioral Biological Biological Availability Black race Blood Cardiometabolic Disease Characteristics Chronic Complex Cross-Sectional Studies DNA Methylation Data Data Set Development Diabetes Mellitus Diagnosis Diet Early identification Educational Status Elderly Enrollment Environment Epigenetic Process Ethnic group Etiology Exposure to Filipino Gene Expression Genes Genetic Transcription Glycosylated hemoglobin A Goals Hawaii Health Health behavior High Prevalence Hispanic Immunologic Factors Incidence Income Indigenous Individual Inflammation Inflammation Mediators Inflammatory Joints Life Style Measures Mediating Medical Metabolic Pathway Modeling Native Americans Native Hawaiian or Other Pacific Islander Neighborhood Health Center Neighborhoods Non-Insulin-Dependent Diabetes Mellitus Outcome Outcome Study Participant Pathway interactions Persons Plasma Population Poverty Prediabetes syndrome Prevalence Prevention strategy Research Research Design Risk Risk Factors Social Environment Social Network Socioeconomic Status System Testing Youth base cohort deprivation diabetes risk diabetic dysbiosis early onset emerging adult epigenetic regulation epigenomics experience follow-up genome-wide glycemic control gut microbiome health disparity health disparity populations health inequalities high risk population immune function improved indigenous community insight lifestyle intervention low socioeconomic status medically underserved microbiome composition monocyte multidisciplinary non-diabetic novel prospective racial and ethnic recruit segregation social social culture social engagement social factors social influence systemic inflammatory response trait underserved community

项目摘要

PROJECT SUMMARY/ABSTRACT Native Hawaiians and Pacific Islanders (NHPIs) experience a disproportionately higher prevalence of cardiometabolic diseases, primarily Type-2 diabetes mellitus (DM), than other U.S. racial/ethnic populations. Compared to White residents, NHPIs have a ~2.5-fold higher incidence and earlier onset of diagnosed DM with significant differences in DM disparities appearing at age 35. NHPIs also have the lowest levels of educational attainment, lowest mean income, highest rates of poverty, and higher exposures to DM risk factors compared to other major racial/ethnic groups in Hawaii, and also reside in environments that include low neighborhood socioeconomic status (nSES). The coincidence of disparities in DM prevalence and adverse social environments implicate complex interactions that may impact gene pathways relevant to the onset of DM. However, the interactions between the social environment and biological mechanism(s) that underlie DM health disparities of NHPIs are unknown. The detrimental effects of social environments, such as nSES, may include an increased prevalence of chronic low-grade inflammation known to contribute to DM. Epigenetic mechanisms (e.g. DNA methylation) regulate transcription of pro-inflammatory genes of monocytes, a key mediator of inflammation. Our preliminary data in NHPIs with DM that completed a lifestyle intervention revealed significant genome-wide changes to the DNA methylation and gene expression states of pro-inflammatory genes that were associated with their monocyte inflammatory activity and glycemic control. In another study, we observed significant changes to the gut microbiome, dysbiosis of which may also be an underlying attribute of DM, in NHPI youth that correlated with social network influences and health behaviors that modified their risk for DM. Lifestyle- associated changes to the gut microbiome impacts DNA methylation through bioavailability of substrates essential to the epigenetic machinery. Thus, we propose a hypothesis that the social environment conditions the epigenomic landscape and gut microbiome composition that regulate inflammation and metabolic pathways underlying DM. To test this hypothesis, we aim to identify an epigenetic signature of DM risk in monocytes from a new cohort of NHPIs and that of their social networks, and examine associations with neighborhood- and interpersonal-level social factors using a cross-sectional study design (Aim 1). We will then explore the mechanistic basis to which this signature may underlie innate DM-relevant traits by examining associations with inflammation, inflammatory activity, and gut microbiome composition/diversity (Aim 2). Finally, we will determine the degree to which this signature may prospectively be predictive of DM outcome (Aim 3). Addressing these aims will yield novel datasets of NHPIs in a health disparate population for determining the relationship between the “immunoepigenetic-gut microbiome axis” and DM risk within the context of the social environment and provide new insight into the etiology of DM disparities in NHPIs, with generalizable implications for improving early identification of DM to enable preventative strategies in populations suffering from social/health inequities.

项目总结/文摘