Potential causal roles of genetically predicted inflammatory factors in hypertrophic scar formation: A two-sample Mendelian randomization study
Wenjun Zhu, Yanan He, Chunhui Xu, Weilin Cai, Jiang Wu, Yue Liu, Junyi Nie, Jing Chen, Quanwen Gao, Liming Liang, Weijie Gu, Lixia ZhangAbstract
Background:
Although correlative evidence from observational research points toward an involvement of inflammatory molecules in hypertrophic scar formation, the concrete causal roles and mechanisms linking these elements have not yet been definitively proven.
Objectives:
This study aimed to explore the potential causal relationship between genetically predicted inflammatory factors and hypertrophic scars using a two-sample Mendelian randomization (MR) approach.
Methods:
We employed a two-sample MR design using summary statistics from genome-wide association studies for inflammatory factors and hypertrophic scars. The primary MR analysis method was inverse variance weighted (IVW). Additional methods included weighted median, weighted mode, and MR-Egger regression analyses. Robust causal estimates were assessed through sensitivity analyses, incorporating MR-Egger intercept tests, MR-PRESSO, Cochran’s Q test, and leave-one-out procedures.
Results:
IVW analysis revealed significant evidence for a causal association between CCL27 (odds ratio [OR] =1.256, 95% confidence interval [CI]: 1.020–1.545), macrophage inflammatory protein-1 beta (MIP-1β) (OR = 0.849, 95% CI: 0.732–0.984), and interleukin-2 (IL-2) (OR = 1.422, 95% CI: 1.012–1.998) with hypertrophic scarring. However, these associations did not remain significant after false discovery rate correction and were not consistently supported by other MR methods (
Conclusion:
This study contributes preliminary causal insights into the role of inflammation in hypertrophic scar formation by hinting at possible associations for CCL27, MIP-1β, and IL-2, but these signals were attenuated upon further testing and should therefore be interpreted with caution. The results warrant further mechanistic investigation to better understand scar pathogenesis and potentially inform targeted interventions.