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Association between circulating inflammatory proteins and gout: A Mendelian randomization study.

Xiaochao Xie1,2, Yanjie Song3, Wenwen Chen2

  • 1Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China.

Medicine
|May 19, 2025
PubMed
Summary

This study used Mendelian randomization to investigate causal links between cytokines, chemokines, and growth factors (CIPs) and gout. Key CIPs like FGF-21 and MMP-1 are implicated in gout development, while gout affects others.

Keywords:
Mendelian randomizationbidirectionalcirculating inflammatory proteinsgoutmeta-analysis

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Area of Science:

  • Immunology
  • Genetics
  • Epidemiology

Background:

  • Inflammation is central to gout pathophysiology and progression.
  • Understanding causal factors influencing gout is crucial for developing effective treatments.

Purpose of the Study:

  • To explore the causal relationship between cytokines, chemokines, and growth factors (CIPs) and gout.
  • To identify specific CIPs involved in gout pathogenesis using Mendelian randomization.

Main Methods:

  • Utilized genome-wide association study (GWAS) data for gout (3576 cases, 147,221 controls).
  • Extracted 132 CIPs and identified single nucleotide polymorphisms (SNPs) associated with gout.
  • Employed the Inverse Variance Weighted (IVW) method for Mendelian randomization analysis.
  • Conducted sensitivity analyses to assess pleiotropy and heterogeneity.

Main Results:

  • Mendelian randomization identified significant associations between several CIPs and gout in European populations.
  • Fibroblast growth factor 21 (FGF-21), matrix metalloproteinase 1 (MMP-1), granulocyte colony-stimulating factor (G-CSF), and interferon-gamma (IFN-γ) are implicated in gout pathogenesis.
  • Gout was found to potentially influence the expression of CXCL1, IL-1 receptor antagonist (IL-1Ra), and tumor necrosis factor-alpha (TNF-α).

Conclusions:

  • Specific CIPs are causally linked to the development and progression of gout.
  • Identifying these CIPs offers potential therapeutic targets for gout treatment and prevention.
  • Further research into these CIPs could elucidate gout's underlying inflammatory mechanisms.