Circulating Cytokine Levels and the Risk of Hypertrophic Scar: A Two‐Sample Mendelian Randomization Study

Background: Chronic inflammation has been implicated in hypertrophic scar (HS) formation based on experimental evidence and clinical observations. However, the existence of a causal relationship between circulating cytokines and the risk of HS remains uncertain. This study aimed to elucidate whether genetically predicted circulating cytokine levels are associated with HS risk using a two‐sample Mendelian randomization (MR) analysis. Methods: We used genetic variants associated with circulating levels of cytokines in a genome‐wide association study (GWAS) meta‐analysis involving 8293 European populations as instrumental variables. HS data were obtained from an open GWAS dataset comprising 208,248 individuals of European descent, including 766 diagnosed HS cases and 207,482 controls. Analysis was performed using MR methods including inverse‐variance weighted (IVW), MR‐Egger, weighted median, simple median, and weighted mode. The MR‐Egger intercept and Cochran’s Q test were applied to assess pleiotropy and heterogeneity, and MR Steiger test was employed to examine the causative direction. Results: Our findings revealed a suggestive causal relationship between elevated circulating levels of interleukin‐2 (IL‐2) and an increased risk of HS (OR: 1.48, 95% CI: 1.04–2.10, p = 0.028); platelet‐derived growth factor‐BB (PDGFbb) was also causally associated with the risk of HS (OR: 1.38, 95% CI: 1.07–1.77, p = 0.012). Conclusion: Our MR analysis provides suggestive evidence supporting a potential causal relationship between circulating IL‐2, PDGFbb, and HS risk. Further research is warranted to explore how these cytokines influence the development of HS.