# Functional and Integrative Omics of Recurrent Gout Flares

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $166,662

## Abstract

PROJECT SUMMARY
Gout is prevalent in the US (3.9% of the adult population) and not only directly impacts peoples’ lives but is also
co-morbid with cardiometabolic disease. Gout consists of unpredictable episodes of acute inflammation or flares
resulting from monocyte NLRP3 inflammasome activation by monosodium urate (MSU) crystals in people with
hyperuricemia, the subsequent production of IL-1, and recruitment of large numbers of inflammatory cells into
the affected joint.
Altered gene expression and DNA methylation in response to MSU crystals in immune cells (neutrophils,
macrophages and monocytes) are key mechanisms underpinning this immune response. In the parent grant to
this supplement we ask two 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? Here, in this diversity supplement, we
will link these expression and methylation differences in immune cells and whole blood to genetic variants
(quantitative trait loci (QTL)) and assign regulatory function to these genetic variants and their target genes
causal in the gout-flare and MSU crystal response.
In Aim 1 RNA-sequencing and whole genome genotyping and methylation data from two datasets (Gout Registry
and Stop Gout) will be used to identify gout-specific blood and immune-cell gene expression QTL (eQTL) and
methylation QTL (meQTL). In Aim 2 we will use experimental systems, including a zebrafish model of gene
regulation, to understand where gout-relevant gene regulatory regions are expressed, if the genetic variants alter
regulatory function and how the target genes might influence the MSU-induced immune response.
Our studies will deepen our knowledge of the mechanisms of gout flares and its genetic basis, and ultimately
point to areas of research that may allow for novel treatments in gout.

## Key facts

- **NIH application ID:** 10629508
- **Project number:** 3R01AR077927-03S1
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** JEFFREY C EDBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $166,662
- **Award type:** 3
- **Project period:** 2020-09-25 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10629508

## Citation

> US National Institutes of Health, RePORTER application 10629508, Functional and Integrative Omics of Recurrent Gout Flares (3R01AR077927-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10629508. Licensed CC0.

---

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