Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 1;159(3):275-280.
doi: 10.1001/jamadermatol.2022.6051.

Association of Lipid-Lowering Drugs With Risk of Psoriasis: A Mendelian Randomization Study

Sizheng Steven Zhao  1 , Zenas Z N Yiu  2 , Anne Barton  3 , John Bowes  3
Affiliations

Association of Lipid-Lowering Drugs With Risk of Psoriasis: A Mendelian Randomization Study

Sizheng Steven Zhao et al. JAMA Dermatol. .

Erratum in

  • Error in Figure 1.
    [No authors listed] [No authors listed] JAMA Dermatol. 2023 Mar 1;159(3):344. doi: 10.1001/jamadermatol.2023.0470. JAMA Dermatol. 2023. PMID: 36920313 Free PMC article. No abstract available.

Abstract

Importance: Lipid pathways have been implicated in the pathogenesis of psoriasis, and some lipid-lowering drugs, such as statins, are hypothesized to have disease-modifying properties. However, large population-level studies are scarce, and causal interpretation of results from traditional observational designs is limited by confounding.

Objective: To investigate the causal association between genetically proxied lipid-lowering drugs and psoriasis risk.

Design, setting, and participants: This 2-sample mendelian randomization study was performed from August to October 2022 and included population-level genome-wide association studies of psoriasis in the UK Biobank and FinnGen studies and low-density lipoprotein (LDL) by the Global Lipids Genetics Consortium. The inverse variance-weighted method was used with pleiotropy robust methods and colocalization as sensitivity analyses.

Exposures: Genetically proxied inhibition of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR, targeted by statins), Niemann-Pick C1-like 1 (NPC1L1, targeted by ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9, targeted by, eg, alirocumab), using LDL as the biomarker.

Main outcomes and measures: Risk of psoriasis.

Results: Data from 12 116 patients with psoriasis and approximately 1.3 million individuals with LDL measurement were analyzed. Genetically proxied PCSK9 inhibition was associated with reduced risk of psoriasis (odds ratio, 0.69 per standard deviation reduction in LDL; 95% CI, 0.55-0.88; P = .003), which was replicated in FinnGen (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002). Sensitivity analyses did not provide statistical evidence of bias from pleiotropy or genetic confounding. No robust association was found for HMGCR or NPC1L1 inhibition.

Conclusions and relevance: This mendelian randomization study suggests that PCSK9 is implicated in psoriasis pathogenesis, and its inhibition is associated with reduced psoriasis risk. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of psoriasis.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Zhao reported personal fees from UCB outside the submitted work. Dr Barton reported grants from Versus Arthritis and the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre during the conduct of the study as well as grants from Bristol Myers Squibb, Galapagos, and Pfizer and personal fees from Chugai Roche outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Associations Between Genetically Proxied Lipid-Lowering Drugs and Psoriasis Risk
HMGCR indicates 3-hydroxy-3-methylglutaryl CoA reductase; LDL, low-density lipoprotein; NPC1L1, Niemann-Pick C1–like 1; OR, odds ratio; PCSK9, proprotein convertase subtilisin/kexin type 9; UKB, UK Biobank.
Figure 2.
Figure 2.. Summary of Psoriasis Risk Results From Pleiotropy Robust Sensitivity Analyses
HMGCR indicates 3-hydroxy-3-methylglutaryl CoA reductase; IVW, inverse variance–weighted method; LDL, low-density lipoprotein; MR, mendelian randomization; NPC1L1, Niemann-Pick C1–like 1; PCSK9, proprotein convertase subtilisin/kexin type 9.
Figure 3.
Figure 3.. Associations Between Genetically Proxied Lipid-Lowering Drugs and Risk of Coronary Artery Disease as the Positive Control
HMGCR indicates 3-hydroxy-3-methylglutaryl CoA reductase; LDL, low-density lipoprotein; NPC1L1, Niemann-Pick C1–like 1; OR, odds ratio; PCSK9, proprotein convertase subtilisin/kexin type 9.
See this image and copyright information in PMC

References

    1. Miller IM, Ellervik C, Yazdanyar S, Jemec GBE. Meta-analysis of psoriasis, cardiovascular disease, and associated risk factors. J Am Acad Dermatol. 2013;69(6):1014-1024. doi:10.1016/j.jaad.2013.06.053 - DOI - PubMed
    1. Friedewald VE, Cather JC, Gelfand JM, et al. . AJC editor’s consensus: psoriasis and coronary artery disease. Am J Cardiol. 2008;102(12):1631-1643. doi:10.1016/j.amjcard.2008.10.004 - DOI - PubMed
    1. Elmets CA, Leonardi CL, Davis DMR, et al. . Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019;80(4):1073-1113. doi:10.1016/j.jaad.2018.11.058 - DOI - PubMed
    1. Socha M, Pietrzak A, Grywalska E, et al. . The effect of statins on psoriasis severity: a meta-analysis of randomized clinical trials. Arch Med Sci. 2019;16(1):1-7. doi:10.5114/aoms.2019.90343 - DOI - PMC - PubMed
    1. Luan C, Chen X, Zhu Y, et al. . Potentiation of psoriasis-like inflammation by PCSK9. J Invest Dermatol. 2019;139(4):859-867. doi:10.1016/j.jid.2018.07.046 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances