Repurposing lipid-lowering drugs as potential treatment for acne vulgaris: a Mendelian randomization study

Background Acne vulgaris, a chronic inflammatory skin condition predominantly seen in teenagers, impacts more than 640 million people worldwide. The potential use of lipid-lowering medications as a treatment for acne vulgaris remains underexplored. This study seeks to investigate the impact of lipid-lowering therapies on the risk of developing acne vulgaris using two-sample Mendelian randomization (MR) analysis.Method The two-sample MR method was employed for analysis, and information on lipid-lowering drugs was obtained from the DrugBank and ChEMBL databases. The summary data for blood low-density lipoprotein (LDL) and triglycerides were sourced from the Global Lipids Genetics Consortium, while genome-wide association studies (GWAS) summary data for acne vulgaris were obtained from the FinnGen database. Heterogeneity was examined using the Q-test, horizontal pleiotropy was assessed using MR-Presso, and the robustness of analysis results was evaluated using leave-one-out analysis.Results The MR analysis provided robust evidence for an association between lowering LDL cholesterol through two drug targets and acne vulgaris, with PCSK9 showing an odds ratio (OR) of 1.782 (95%CI: 1.129-2.812, p = 0.013) and LDL receptor (LDLR) with an OR of 1.581 (95%CI: 1.071-2.334, p = 0.021). Similarly, targeting the lowering of triglycerides through lipoprotein lipase (LPL) was significantly associated with an increased risk of acne vulgaris, indicated by an OR of 1.607 (95%CI: 1.124-2.299, p = 0.009).Conclusion The current MR study presented suggestive evidence of a positive association between drugs targeting three genes (PCSK9, LDLR, and LPL) to lower lipids and a reduced risk of acne vulgaris.