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Inflammatory cytokine profiles in erectile dysfunction: a bidirectional Mendelian randomization.

Dongze Liu1, Zheng Qin2, Bocun Yi1

  • 1Department of Urology, National Key Specialty of Urology, Second Hospital of Tianjin Medical University, Tianjin Key Institute of Urology, Tianjin Medical University, Tianjin, China.

Frontiers in Immunology
|April 29, 2024
PubMed
Summary

Interferon-inducible protein-10 (IP-10) increases erectile dysfunction (ED) risk, while interleukin-1 receptor antagonist (IL-1RA) decreases it. These inflammatory cytokines offer potential targets for ED treatment and prevention.

Keywords:
IL-1raIP-10bidirectional Mendelian randomizationerectile dysfunctioninflammatory cytokine

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Area of Science:

  • Genetics
  • Immunology
  • Urology

Background:

  • Inflammatory cytokines (ICs) are implicated in erectile dysfunction (ED).
  • Elevated levels of TNF-α, IL-6, and IL-8 are observed in many ED patients.
  • The causal relationship between specific ICs and ED requires further investigation.

Purpose of the Study:

  • To investigate the causal relationship between 41 inflammatory cytokines (ICs) and erectile dysfunction (ED).
  • To identify specific ICs that influence ED risk using a Mendelian randomization (MR) approach.

Main Methods:

  • Utilized genome-wide association study (GWAS) data for 41 ICs from 8293 subjects.
  • Employed the FINNGEN R9 database for ED outcome data (2205 cases, 164104 controls).
  • Applied MR-Egger, inverse variance weighting (IVW), and weighted median (WM) methods, with IVW as the primary analysis.

Main Results:

  • Increased interferon-inducible protein-10 (IP-10) levels significantly elevated ED risk (OR=1.269, P=0.043).
  • Increased interleukin-1 receptor antagonist (IL-1RA) levels significantly decreased ED risk (OR=0.768, P=0.037).
  • Reverse MR analysis did not confirm causality for IP-10 or IL-1RA.

Conclusions:

  • Inflammatory cytokines significantly impact ED risk, with IP-10 acting as a risk factor and IL-1RA as a protective factor.
  • Targeted intervention with specific inflammatory factors presents a potential strategy for ED treatment and prevention.