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

TL;DR

This study investigates the causal link between inflammatory factors and hypertrophic scars using genetic data and finds a potential role for CTACK in scar formation.

Contribution

The study provides novel causal evidence linking CTACK to hypertrophic scars using Mendelian randomization.

Findings

CTACK shows a significant causal association with hypertrophic scars (OR 1.21, p=0.01) using IVW method.

Other inflammatory factors like IL-1β, TNFα, and IL-8 do not show significant associations with scar risk.

MR-Egger and PRESSO analyses suggest no major pleiotropy, except for RANTES, which becomes non-significant after outlier removal.

Abstract

Hypertrophic scars result from abnormal healing following skin injuries.

To delve deeper into the causal association between inflammatory factors and hypertrophic scars.

This study utilized genetic data from the FINN cohort and pertinent literature to scrutinize the nexus between a spectrum of inflammatory factors—encompassing IL‐1β, interleukin 1 receptor‐like 1, MCP1, RANTES/CCL5, TNFα, IL‐8, IL‐18, and CTACK/CCL27—and the risk of hypertrophic scarring. Our analytical strategy was based on the inverse variance weighted (IVW) approach, further bolstered by MR‐Egger, weighted median, and weighted mode methods to ensure a comprehensive assessment. The reliability of our findings was rigorously appraised through Cochran's Q test, MR‐Egger regression, MR‐PRESSO, and leave‐one‐out analysis.

The genetic prediction results revealed a significant association between CTACK and hypertrophic scars (OR 1.21, 95% CI 1.05–1.4, p = 0.01) using the IVW method, although it was not corroborated by other MR analysis methods. The remaining inflammatory factors did not exhibit significant correlations with the risk of hypertrophic scar formation (all p > 0.05). The absence of significant heterogeneity among the IVs was indicated by Cochran's Q test. MR‐Egger and MR‐PRESSO analyses collectively suggested no substantial horizontal pleiotropy influencing the results, except for the relationship between RANTES and hypertrophic scars. Upon exclusion of an outlier, the causal relationship between RANTES and hypertrophic scars was found to be non‐significant.

Our MR analysis supports a causal association between CTACK and hypertrophic scars, enhancing our understanding of scar formation and suggesting potential targeted therapeutic strategies for treatment.

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