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:
- 金额:$ 66.79万
- 依托单位:
- 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:
- 关键词:AddressAdultAffectAgeBehavioralBiologicalBiological AvailabilityBlack raceBloodCardiometabolic DiseaseCharacteristicsChronicComplexCross-Sectional StudiesDNA MethylationDataData SetDevelopmentDiabetes MellitusDiagnosisDietDisparityEarly identificationEducational StatusElderlyEnrollmentEnvironmentEpigenetic ProcessEthnic PopulationEtiologyExposure toFilipinoGene ExpressionGenesGenetic TranscriptionGlycosylated hemoglobin AGoalsHawaiiHealthHealth behaviorHigh PrevalenceHispanicImmunologic FactorsIncidenceIncomeIndigenousIndividualInequityInflammationInflammation MediatorsInflammatoryJointsLife StyleMeasuresMediatingMedicalMetabolic PathwayModelingNative AmericansNative Hawaiian or Other Pacific IslanderNeighborhood Health CenterNeighborhoodsNon-Insulin-Dependent Diabetes MellitusOutcomeOutcome StudyParticipantPathway interactionsPersonsPlasmaPopulationPovertyPrediabetes syndromePrevalencePrevention strategyQualifyingRaceResearchResearch DesignRiskRisk FactorsSocial EnvironmentSocial NetworkSocioeconomic StatusSystemTestingYouthcohortdeprivationdiabetes riskdiabeticdysbiosisearly onsetemerging adultepigenetic regulationepigenomicsexperiencefollow-upgenome-wideglycemic controlgut microbiomehealth disparityhealth disparity populationshealth inequalitieshigh risk populationimmune functionimprovedindigenous communityinsightlifestyle interventionlow socioeconomic statusmedically underservedmicrobiome compositionmonocytemultidisciplinarynon-diabeticnovelprospectiveracial populationrecruitsegregationsocialsocial culturesocial engagementsocial factorssocial influencesystemic inflammatory responsetraitunderserved 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(NHPI)经历了不成比例的高发病率
心脏代谢性疾病,主要是2型糖尿病(DM),比美国其他种族/民族人群更容易患上。
与白人居民相比,NHPI的发病率高出约2.5倍,被诊断为糖尿病的患者发病更早
糖尿病差异在35岁时出现显著差异。NHPI的教育水平也是最低的
最低平均收入、最高贫困率和更高的糖尿病风险因素风险暴露
夏威夷的其他主要种族/民族群体,也居住在包括低社区在内的环境中
社会经济地位(NSE)。糖尿病患病率差异与不利社会环境的重合
涉及复杂的相互作用,可能影响与糖尿病发病相关的基因通路。然而,
糖尿病健康差距形成的社会环境与生物机制的相互作用(S)
NHPI是未知的。社会环境的有害影响,如NSE,可能包括增加
已知的与糖尿病有关的慢性低度炎症的流行。表观遗传机制(例如DNA
甲基化)调节单核细胞致炎基因的转录,单核细胞是炎症的关键介质。我们的
在完成生活方式干预的糖尿病患者的NHPI中的初步数据显示,全基因组显著
致炎相关基因DNA甲基化和基因表达状态的变化
单核细胞的炎症活性和血糖控制。在另一项研究中,我们观察到显著的
在NHPI青年中,肠道微生物群的变化,其微生物群落的失调也可能是DM的一个潜在属性
与社会网络影响和健康行为相关,从而改变了他们患糖尿病的风险。生活方式-
肠道微生物群的相关变化通过底物的生物利用度影响DNA甲基化
对于表观遗传机制来说是必不可少的。因此,我们提出了一个假设,即社会环境条件
调控炎症和代谢途径的表观基因组图景和肠道微生物组组成
潜在DM。为了验证这一假设,我们的目标是在单核细胞中识别DM风险的表观遗传学特征。
一组新的NHPI及其社交网络,并检查与邻居和
采用横断面研究设计的人际层面的社会因素(目标1)。然后我们将探索
这一特征可能构成先天糖尿病相关特征的机制基础,通过检查与
炎症、炎症活动和肠道微生物群组成/多样性(目标2)。最后,我们将确定
这一特征对糖尿病预后的预测性程度(目标3)。解决这些问题
AIMS将在健康不同的人群中产生新的NHPI数据集,以确定两者之间的关系
“免疫表观遗传-肠道微生物组轴”和糖尿病风险在社会环境和
对健康保险指标中糖尿病差异的病因提供了新的见解,并对改进具有普遍意义
及早发现糖尿病,以便在遭受社会/健康不平等之苦的人群中采取预防策略。
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)
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。
- DOI:10.1177/15248399231190356
- 发表时间:2023
- 期刊:
- 影响因子:1.9
- 作者:Maunakea,AlikaK;Juarez,Ruben;Maunakea-Forth,JKukui
- 通讯作者:Maunakea-Forth,JKukui
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:
- 影响因子:1.9
- 作者:Jernigan,ValarieBlueBird;Demientieff,LaVerneXilegg;Maunakea,AlikaK
- 通讯作者:Maunakea,AlikaK
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:
- 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.
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:
- 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.
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Alika Keolaokalani Maunakea其他文献
Alika Keolaokalani Maunakea的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Alika Keolaokalani Maunakea', 18)}}的其他基金
Consortium of Research Advancement Facilities and Training
研究进步设施和培训联盟
- 批准号:
10594452 - 财政年份:2022
- 资助金额:
$ 66.79万 - 项目类别:
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
- 批准号:
10458062 - 财政年份:2021
- 资助金额:
$ 66.79万 - 项目类别:
Community Driven Approach to Mitigate COVID 19 Disparities in Hawaii's Vulnerable Populations
社区驱动的方法来减少夏威夷弱势群体中的 COVID 19 差异
- 批准号:
10257492 - 财政年份:2020
- 资助金额:
$ 66.79万 - 项目类别:
Immunoepigenetic-gut microbiome axis in the social networks of health disparate youth
健康不同青年社交网络中的免疫表观遗传-肠道微生物组轴
- 批准号:
10022453 - 财政年份:2019
- 资助金额:
$ 66.79万 - 项目类别:
Epigenomic Conditioning of Monocyte Inflammatory Activity in Native Hawaiians with Diabetes
夏威夷原住民糖尿病患者单核细胞炎症活动的表观基因组调节
- 批准号:
10000972 - 财政年份:2019
- 资助金额:
$ 66.79万 - 项目类别:
Epigenomic Dysregulation of Neurodevelopmental Genes Underlies Autism Spectrum Disorders
神经发育基因的表观基因组失调是自闭症谱系障碍的基础
- 批准号:
9370571 - 财政年份:2017
- 资助金额:
$ 66.79万 - 项目类别:
Epigenomic Dysregulation of Neurodevelopmental Genes Underlies Autism Spectrum Disorders
神经发育基因的表观基因组失调是自闭症谱系障碍的基础
- 批准号:
9552273 - 财政年份:2017
- 资助金额:
$ 66.79万 - 项目类别:
Identifying Epigenetic Biomarkers of Cardiovascular Disease Risk In Humans
识别人类心血管疾病风险的表观遗传生物标志物
- 批准号:
9198044 - 财政年份:2014
- 资助金额:
$ 66.79万 - 项目类别:
Identifying epigenetic biomarkers of cardiovascular disease risk in humans
识别人类心血管疾病风险的表观遗传生物标志物
- 批准号:
8803666 - 财政年份:2014
- 资助金额:
$ 66.79万 - 项目类别:
The Contribution of CpG Island Methylation to the Tissue-Specific Expression of S
CpG 岛甲基化对 S 组织特异性表达的贡献
- 批准号:
7081283 - 财政年份:2005
- 资助金额:
$ 66.79万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 66.79万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 66.79万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 66.79万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 66.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 66.79万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 66.79万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 66.79万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 66.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 66.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 66.79万 - 项目类别:
Grant-in-Aid for Scientific Research (C)