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ORIGINAL RESEARCH article

Front. Med.
Sec. Dermatology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1396036

Causal effects of lipid-lowering drugs on skin diseases: a two-sample Mendelian randomization study

Provisionally accepted
Yong Liu Yong Liu 1*Hui Liu Hui Liu 2Queqiao Bian Queqiao Bian 1
  • 1 The Third Central Hospital of Tianjin, Tianjin, China
  • 2 Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin, China

The final, formatted version of the article will be published soon.

    Background: Although previous studies have indicated an association between lowdensity lipoprotein (LDL) and skin diseases, their causal effects remain inconclusive.This study aimed to assess the causal relationship between genetically proxied lipidlowering drugs and skin cancers and psoriasis.Methods: Two-sample Mendelian randomization (MR) analysis was performed using single-nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was used to determine causal relationships. The "leave-one-out" sensitivity test, Cochran's Q-statistic and MR-Egger intercept were used to assess heterogeneity and horizontal pleiotropy.We identified 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and proprotein convertase subtilisin-kexin type 9 (PCSK9) as genetically proxied lipidlowering drugs. Genetically proxied inhibition of HMGCR (stains) was causally associated with reduced risk of nonmelanoma skin cancer (OR 0.982, 95% CI 0.967-0.997, p = 0.016 by weighted median; OR 0.977, 95% CI 0.966-0.989, p < 0.001 by IVW) and psoriasis (OR 0.585, 95% CI 0.378-0.905, p = 0.016 by IVW), while PCSK9 inhibition (alirocumab) was causally associated with reduced risk of psoriasis (OR 0.560, 95% CI 0.413-0.761 by weighted median; OR 0.564, 95% CI 0.447-0.712 by IVW; p < 0.001) in the ieu-b-5089 dataset. Similar results were observed in the ieu-b-110 dataset for HMGCR and PCSK9. Sensitivity analysis revealed no evidence of heterogeneity or horizontal pleiotropy.This study revealed the existing HMGCR inhibitors (stains) might be protective for reducing nonmelanoma skin cancer risk, and HMGCR inhibitors (stains) and PCSK9 inhibitor (alirocumab) might be promising for reducing psoriasis risk in the European population.

    Keywords: Mendelian randomization study, single-nucleotide polymorphisms, genome-wide association studies, Lipid-lowering drugs, Psoriasis, melanoma skin cancer, Nonmelanoma skin cancer

    Received: 09 Mar 2024; Accepted: 13 Sep 2024.

    Copyright: © 2024 Liu, Liu and Bian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yong Liu, The Third Central Hospital of Tianjin, Tianjin, China

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