# Identifying Novel Biological Pathways for Gout using DNA Methylation and Genetics

> **NIH NIH R01** · UNIVERSITY OF MISSISSIPPI MED CTR · 2021 · $464,493

## Abstract

Abstract: Identifying Novel Biological Pathways for Gout using DNA Methylation and Genetics
Gout is the most common form of inflammatory arthritis and affects ~8 million U.S. adults. Patients with gout
experience intensely painful flares associated with impaired quality of life and high levels of healthcare
utilization. With increasing prevalence of risk factors for gout, such as older age, obesity, hypertension, chronic
kidney disease, and hyperuricemia, the incidence and prevalence of gout and its public health
importance are all rising. However, gout is understudied compared to other rheumatologic conditions.
Discovery of novel risk factors for gout can enhance our understanding of the disease susceptibility and
identify targets for prevention and treatment. Gout attacks are inflammatory responses to the deposition of
monosodium urate crystals in articular tissues causing rapidly intensifying painful and swollen joint(s).
However, most individuals with hyperuricemia do not development gout. Our understanding of individual
variation in susceptibility to acute gout is limited. The immune response is known to be involved in gout flares,
including activation of the inflammasome. Emerging evidence supports links between inflammation and DNA
methylation levels. However, factors influencing DNA methylation levels and their consequences for chronic
disease remain to be elucidated. The examination of DNA methylation in whole blood has the potential to
uncover epigenetic risk factor for gout. DNA methylation levels may also be intermediaries of environmental
and genetic risk factors for gout and thus could yield insight into the biological pathways mediating gout flares
or may serve as biomarkers for exposure to environmental risk factors. The overarching goal of this study is
to uncover epigenetic factors that can illuminate the biological pathways underlying gout susceptibility
and/or serve as biomarkers for the prediction of gout. Our aims are : (1) to identify DNA methylation sites
associated with incident gout; (2) to identify DNA methylation sites associated with serum urate levels followed
by (i) evaluating the potential causal relation between associated DNA methylation sites and serum urate using
a Mendelian randomization approach, and (ii) an in-depth investigation of the urate-associated sites that have
been linked to blood pressure; (3) to develop and validate risk prediction models for gout incorporating data
from: (i) clinical, (ii) genetic and (iii) epigenetic risk factors, and examine how factors beyond serum urate levels
add to risk prediction across sexes and over intermediate and longer time periods. This proposed study will
accelerate research on gout prevention and treatment by identifying potentially reversible epigenetic factors
related to incident gout and urate levels. The gout risk prediction models will lay the foundation for risk
stratification strategy for future intervention trials for gout treatment and management, particu...

## Key facts

- **NIH application ID:** 10058810
- **Project number:** 5R01AR073178-04
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** ADRIENNE TIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $464,493
- **Award type:** 5
- **Project period:** 2018-09-21 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058810

## Citation

> US National Institutes of Health, RePORTER application 10058810, Identifying Novel Biological Pathways for Gout using DNA Methylation and Genetics (5R01AR073178-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10058810. Licensed CC0.

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