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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54MD007601-32
Application #
9569302
Study Section
Special Emphasis Panel (ZMD1)
Project Start
Project End
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
32
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Hawaii
Department
Type
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Panee, Jun; Gerschenson, Mariana; Chang, Linda (2018) Associations Between Microbiota, Mitochondrial Function, and Cognition in Chronic Marijuana Users. J Neuroimmune Pharmacol 13:113-122
Guo, Mengjie; Lu, Sicheng; Huang, Hongming et al. (2018) Increased AURKA promotes cell proliferation and predicts poor prognosis in bladder cancer. BMC Syst Biol 12:118
Zhang, Zao; Chew, Glen M; Shikuma, Cecilia M et al. (2018) Red blood cell distribution width as an easily measurable biomarker of persistent inflammation and T cell dysregulation in antiretrovirally treated HIV-infected adults. HIV Clin Trials :1-5
Kim, Sunja; Choi, Seemoon; Chung-Do, Jane J et al. (2018) Comparing Birth Outcomes in Hawai'i between US- and Foreign-Born Women. Hawaii J Med Public Health 77:188-198
Yu, Zongtao; Chen, Hankui; Zhu, Yong et al. (2018) Global lipidomics reveals two plasma lipids as novel biomarkers for the detection of squamous cell lung cancer: A pilot study. Oncol Lett 16:761-768
Siriwardhana, Chathura; Lim, Eunjung; Davis, James et al. (2018) Progression of diabetes, ischemic heart disease, and chronic kidney disease in a three chronic conditions multistate model. BMC Public Health 18:752
Seale, Lucia A; Ogawa-Wong, Ashley N; Berry, Marla J (2018) SEXUAL DIMORPHISM IN SELENIUM METABOLISM AND SELENOPROTEINS. Free Radic Biol Med 127:198-205
Fang, Rui; Zhu, Yong; Khadka, Vedbar S et al. (2018) The Evaluation of Serum Biomarkers for Non-small Cell Lung Cancer (NSCLC) Diagnosis. Front Physiol 9:1710
Gandhi, Krupa; Lim, Eunjung; Davis, James et al. (2018) Racial Disparities in Health Service Utilization Among Medicare Fee-for-Service Beneficiaries Adjusting for Multiple Chronic Conditions. J Aging Health 30:1224-1243
Pirkle, Catherine M; Wu, Yan Yan; Zunzunegui, Maria-Victoria et al. (2018) Model-based recursive partitioning to identify risk clusters for metabolic syndrome and its components: findings from the International Mobility in Aging Study. BMJ Open 8:e018680

Showing the most recent 10 out of 46 publications