# Epigenomic Conditioning of Monocyte Inflammatory Activity in Native Hawaiians with Diabetes

> **NIH NIH R03** · UNIVERSITY OF HAWAII AT MANOA · 2020 · $77,791

## Abstract

PROJECT SUMMARY/ABSTRACT
 A primary goal of this application is to understand the molecular basis of environmental and epigenetic
interactions that consequently influence inflammatory states underlying Type-2 diabetes mellitus (DM). Native
Hawaiians and Pacific Islanders (NHs/PIs) experience a disproportionately higher prevalence and earlier onset
of DM than other ethnic groups. The socioeconomic and lifestyle factors conferring NHs/PIs to the heightened
prevalence of DM associate with altered global levels of DNA methylation, an epigenetic mechanism likely to
play a major role in regulating the chronic low-grade systemic inflammation characteristic of DM. Indeed,
inflammation has been shown to be associated with global DNA hypermethylation in peripheral blood
mononuclear cells (PBMCs), independent of other risk factors for DM. Interestingly, differential DNA
methylation at specific genomic loci in PBMCs exhibited changes at genes related to immune function and
inflammatory pathways, which are associated with biomarkers of inflammation. However, the heterogeneity in
cell type composition of PBMCs makes it difficult to determine how these observed differences in DNA
methylation associate with inflammation. Monocytes play a central role in both acute and chronic inflammation,
secreting various pro-inflammatory cytokines after stimulation with toll like receptor ligands, and are thus a
major source of systemic inflammation. DNA methylation regulates the transcriptional levels of pro-
inflammatory cytokines expressed by monocytes. Together, these studies suggest that the DNA methylation
landscape of monocytes may be associated with inflammatory states of the cells, which may be altered in DM
to correspond with inflammation. We seek to examine this relationship in NHs/PIs, which has never before
been reported. We have collected preliminary data that form the basis for the hypothesis that compared to
healthy individuals, monocytes from NHs/PIs diagnosed with DM exhibit a distinct DNA methylomic landscape,
which conditions their heightened inflammatory response. To address this hypothesis, we propose to access
our Multiethnic Cohort (MEC), from which we have detailed health information, and banked viably
cryopreserved PBMCs and paired plasma biospecimens. We aim to (1) evaluate the relationships between
insulin resistance, systemic inflammation, and ex vivo monocyte inflammatory activity in age- and sex-matched
healthy (n=20) and DM-diagnosed (n=20) NHs/PIs, and (2) characterize and compare the DNA methylomes of
these monocytes, following enrichment from PBMCs, using two independent yet complementary genome-wide
approaches. We anticipate that these results will inform the extent to which the DNA methylomic landscape
may condition monocyte inflammatory activity and how this associates with known risk factors for DM. This
study will form the foundation for future work investigating the extent to which differences in monocyte function
may be attributed to ...

## Key facts

- **NIH application ID:** 10000972
- **Project number:** 5R03HL146886-02
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Alika Keolaokalani Maunakea
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $77,791
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000972

## Citation

> US National Institutes of Health, RePORTER application 10000972, Epigenomic Conditioning of Monocyte Inflammatory Activity in Native Hawaiians with Diabetes (5R03HL146886-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10000972. Licensed CC0.

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