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：
10600080
负责人：
Alika Keolaokalani Maunakea
金额：
$ 66.79万
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/10600080
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 Disparity Early identification Educational Status Elderly Enrollment Environment Epigenetic Process Ethnic Population 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 Inequity 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 Qualifying Race Research Research Design Risk Risk Factors Social Environment Social Network Socioeconomic Status System Testing Youth 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 population 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.

项目摘要/摘要夏威夷原住民和太平洋岛民（NHPIS）的患病率不成比例与其他美国种族/族裔人群相比，心脏代谢疾病，主要2型糖尿病（DM）。与白人居民相比，NHPI的事件高约2.5倍，诊断DM的发作早期发作 35岁时出现的DM分布的显着差异。NHPIS也具有最低的教育水平与DM风险因素相比夏威夷的其他主要种族/族裔群体，也居住在包括低社区的环境中社会经济地位（NSE）。 DM患病率和不利社会环境中分布的巧合暗示可能影响与DM发作相关的基因途径的复杂相互作用。但是，社会环境与生物学机制之间的相互作用，这些机制是DM健康分布的基础 NHPI是未知的。社交环境（例如NSES）的有害影响可能包括增加已知会导致DM的慢性低度炎症的患病率。表观遗传机制（例如DNA 甲基化）调节单核细胞促炎基因的转录，这是炎症的关键介体。我们的 DM完成生活方式干预的NHPI中的初步数据显示出明显的基因组促炎基因的DNA甲基化和基因表达状态的变化其单核细胞炎症活性和血糖控制。在另一项研究中，我们观察到了重要的肠道微生物组的变化，其营养不良也可能是DM的潜在属性，在NHPI青年中与社交网络的影响和健康行为相关，以改变其DM风险。生活方式- 肠道微生物组的相关变化通过底物的生物利用度影响DNA甲基化对表观遗传机制必不可少的。这就是我们提出的一个假设，即社会环境条件调节注射和代谢途径的表观基因组景观和肠道微生物组组成基础DM。为了检验这一假设，我们旨在确定单核细胞中DM风险的表观遗传学特征 NHPI的新队列及其社交网络，并研究与邻里和社区的关联通过横断面研究设计（AIM 1）的人际社会因素。然后，我们将探索通过研究与炎症，炎症活性和肠道微生物组组成/多样性（AIM 2）。最后，我们将确定该签名可能会预测DM结果的程度（AIM 3）。解决这些目标将在健康人群中产生NHPI的新型数据集，以确定在社会环境和对NHPIS中DM分布的病因提供新的见解，对改善早期识别DM以实现患有社会/健康不平等的人群的预防策略。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Food Sovereignty as a Path to Health Equity for Indigenous Communities: Introduction to the Focus Issue.

粮食主权作为土著社区健康公平的途径：焦点问题简介。

DOI：
10.1177/15248399231190355
发表时间：
2023
期刊：
Health promotion practice
影响因子：
1.9
作者：
Jernigan,ValarieBlueBird;Demientieff,LaVerneXilegg;Maunakea,AlikaK
通讯作者：
Maunakea,AlikaK

Examining the immunoepigenetic-gut microbiome axis in the context of self-esteem among Native Hawaiians and other Pacific Islanders.

DOI：
10.3389/fgene.2023.1125217
发表时间：
2023
期刊：
FRONTIERS IN GENETICS
影响因子：
3.7
作者：
Becerra, Celyna Y. Y.;Wells, Riley K. K.;Kunihiro, Braden P. P.;Lee, Rosa H. H.;Umeda, Lesley;Allan, Nina P. P.;Rubas, Noelle C. C.;McCracken, Trevor A. A.;Nunokawa, Chandler K. L.;Lee, Ming-Hao;Pidlaoan, Felix Gerard S.;Phankitnirondorn, Krit;Dye, Christian K. K.;Yamamoto, Brennan Y.;Peres, Rafael;Juarez, Ruben;Maunakea, Alika K. K.
通讯作者：
Maunakea, Alika K. K.

HMGB1 mediates microbiome-immune axis dysregulation underlying reduced neutralization capacity in obesity-related post-acute sequelae of SARS-CoV-2.

DOI：
10.1038/s41598-023-50027-1
发表时间：
2024-01-03
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Rubas, Noelle C.;Peres, Rafael;Kunihiro, Braden P.;Allan, Nina P.;Phankitnirundorn, Krit;Wells, Riley K.;McCraken, Trevor A.;Lee, Rosa H.;Umeda, Lesley;Conching, Andie;Juarez, Ruben;Maunakea, Alika K.
通讯作者：
Maunakea, Alika K.

The Mauli Ola Study: A Unique Academic-Community Partnership With MA'O Organic Farms to Understand and Address Health Inequities Among Native Hawaiians and Other Pacific Islanders in Hawai'i.

Mauli Ola 研究：与 MAO 有机农场建立独特的学术界合作伙伴关系，以了解和解决夏威夷原住民和其他太平洋岛民之间的健康不平等问题。