Genetic Evidence of Obesity-Induced Chronic Wounds Mediated by Inflammatory Biomarkers

<b>Background:</b> Obese patients are increasingly recognized as being at higher risk for skin diseases, particularly chronic wounds. While the exact mechanisms remain unclear, obesity is suspected to influence the development of chronic injuries via inflammatory biomarkers. Single nucleotide polymorphisms (SNPs) may further influence gene expression, protein function, and levels of inflammatory biomarkers through various mechanisms, thereby modulating inflammatory responses that contribute to wound pathogenesis. <b>Methods:</b> A two-sample two-step Mendelian Randomization (MR) was employed to explore the causal relationship between obesity and chronic wounds, focusing on the mediating role of inflammatory biomarkers. SNPs were used as instrumental variables (IVs) to infer causality. Obesity-related genetic data were sourced from the UK Biobank and GIANT consortium. Genome-wide association studies provided data on 92 inflammatory biomarkers, involving 14,824 and 575,531 individuals. Pressure injuries, lower limb venous ulcers, and diabetic foot ulcer data were obtained from FinnGen R10 and the Pan-UK Biobank. <b>Results:</b> Obesity significantly increased the risk of pressure injuries, lower limb venous ulcers, and diabetic foot ulcers. CCL19, hGDNF, IL-12B, and TNFRSF9 were identified as mediators in obesity-induced lower limb venous ulcers. <b>Conclusion:</b> This study provides genetic evidence that obesity leads to lower limb venous ulcers via inflammatory biomarkers, suggesting potential therapeutic targets for intervention.