# Functional and Integrative Omics of Recurrent Gout Flares

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $386,834

## Abstract

PROJECT SUMMARY
Monosodium urate crystals (MSU) activate inflammatory immune cells (e.g. monocytes/neutrophils), which
potentiate acute gout attacks. Ultrasound and dual energy CT scans have shown the presence of MSU crystal
deposits in joints of asymptomatic gout patients. These observations lead experts to agree that other unknown
molecular factors are triggers for gout and recurrent flares. Our ancillary project's aims address two main
questions: 1) Do neutrophils and/or monocytes, upon ex vivo activation by MSU crystals, exhibit gene
expression and DNA methylation differences between gout patients with recurrent gout flares compared to
those that do not? 2) Among gout patients from a clinical trial setting, where treat-to-target urate lowering
therapy (ULT) is administered, are there gene expression and DNA methylation differences from the peripheral
blood between individuals with or without recurrent flares? In aim 1 in a mechanistic/functional approach we
will isolate neutrophils and CD14+ monocytes using fresh samples of peripheral blood from gout patients newly
recruited into UAB's Gout Registry, the time sensitive parent project for this R01. The UAB Gout Registry is
administered by UAB's NIAMS funded Center of Research Translation (CORT) “INvestigationS In Gout,
Hyperuricemia, and comorbidiTies (INSIGHT)” (NIH P50 060772), which is the parent project for our ancillary
study. The cells will be activated with MSU and we will use RNAseq to compare gene expression between
groups (recurrent flares vs no flares). We will determine whether DNA methylation changes may be associated
with observed transcription differences. In aim 2 we will utilize clinical data and biological samples from the
clinical trial, VA-CSP594, the “Stop Gout” trial. The trial is a non-inferiority comparison between the ULT
agents, febuxostat and allopurinol, of the primary outcome, the proportion of participants who flare at least
once. The Stop Gout trial organizers agreed to augment their biospecimen collection to allow the collection of
RNA for our ancillary study. We will analyze ~300 samples of RNA from the trial's participants. We will
compare baseline gene expression and DNA methylation associations with recurrent flares. We will utilize
Mendelian randomization to assess the causality of differentially methylated CpGs and expressed transcripts
with recurrent gout flares. The results from aims 1 and 2 will expand our knowledge of the transcriptomic and
methylomic changes that precipitate gout flares, which will translate to improved gout patient care and
treatment.

## Key facts

- **NIH application ID:** 10693097
- **Project number:** 5R01AR077927-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** JEFFREY C EDBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $386,834
- **Award type:** 5
- **Project period:** 2020-09-25 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693097

## Citation

> US National Institutes of Health, RePORTER application 10693097, Functional and Integrative Omics of Recurrent Gout Flares (5R01AR077927-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10693097. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*