Causal Association Between Inflammatory Factors and Hypertrophic Scar: A Two-Sample Mendelian Randomization Study

Area of Science:

• Genetics
• Immunology
• Dermatology

Background:

• Hypertrophic scars arise from dysregulated healing post-skin injury.
• Inflammatory factors play a role in abnormal scar development.

Purpose of the Study:

• To investigate the causal relationship between specific inflammatory factors and hypertrophic scar risk.
• To identify potential biomarkers and therapeutic targets for hypertrophic scarring.

Main Methods:

• Utilized Mendelian randomization (MR) analysis with genetic data from the FINN cohort.
• Assessed eight inflammatory factors: IL-1β, IL-1Rrp, MCP1, RANTES/CCL5, TNFα, IL-8, IL-18, and CTACK/CCL27.
• Employed IVW, MR-Egger, weighted median, and weighted mode methods, with sensitivity analyses for robustness.

Main Results:

• A significant causal association was found between CTACK/CCL27 and hypertrophic scars (OR 1.21, p=0.01) via IVW, though not consistently across all MR methods.
• No significant causal links were observed for other assessed inflammatory factors.
• Sensitivity analyses indicated minimal horizontal pleiotropy, with no significant association for RANTES/CCL5 after outlier removal.

Conclusions:

• Mendelian randomization analysis supports a causal role for CTACK/CCL27 in hypertrophic scar development.
• Findings enhance understanding of scar pathogenesis and suggest CTACK/CCL27 as a potential therapeutic target.