Rheumatoid arthritis and gout: a rare combination or overlooked coexistence?

Area of Science:

• Rheumatology
• Immunology
• Genetics

Background:

• Rheumatoid arthritis (RA) and gout are often viewed as distinct conditions.
• Emerging evidence suggests a potential underestimation of their co-occurrence.
• This study investigates the epidemiological, genetic, and molecular links between RA and gout.

Purpose of the Study:

• To evaluate the epidemiological association between RA and gout.
• To assess the genetic causality of RA on gout and serum urate levels.
• To identify intersecting molecular features and pathways shared by both diseases.

Main Methods:

• Utilized National Health and Nutrition Examination Survey (NHANES) data for epidemiological analysis.
• Employed Mendelian randomization (MR) with genome-wide association study (GWAS) data for genetic causality assessment.
• Conducted transcriptomic analyses (differential expression, WGCNA) and integrated with disease databases for pathway enrichment.

Main Results:

• RA patients exhibited higher gout prevalence (10.3% vs. 4.8%) with an increasing trend over time.
• RA was identified as an independent risk factor for gout (OR: 2.67).
• MR supported a causal effect of RA on gout, particularly seronegative RA (SNRA), but not on serum urate (SUA).
• Identified 207 shared genes enriched in interferon signaling, immune activation, and antiviral defense pathways, with five hub genes (RSAD2, DDX60, IFIT1, IFIT3, XAF1).

Conclusions:

• RA and gout exhibit a notable overlap, with stronger genetic links in SNRA.
• The association between RA and gout may not be primarily mediated by serum urate pathways.
• Shared transcriptomic profiles in interferon signaling suggest convergent molecular mechanisms warranting further research.