The association between ACE inhibitors and psoriasis based on the drug-targeted Mendelian randomization and real-world pharmacovigilance analyses

ABSTRACT

Background

Although a growing number of observational studies suggest that angiotensin-converting enzyme inhibitors (ACEIs) intake may be a risk factor for psoriasis, evidence is still insufficient to draw definitive conclusions.

Research design and methods

Drug-targeted Mendelian randomization (DTMR) was used to analyze the causality between genetic proxied ACEIs and psoriasis. Furthermore, we performed a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database to identify more suspicious subclasses of ACEIs.

Results

Using two kinds of genetic proxy instruments, the present DTMR research identified genetic proxied ACEIs as risk factors for psoriasis. Furthermore, our disproportionality analysis revealed that ramipril, trandolapril, perindopril, lisinopril, and enalapril were associated with the risk of psoriasis, which validates and refines the findings of the DTMR.

Conclusions

Our integrative study verified that ACEIs, especially ramipril, trandolapril, perindopril, lisinopril, and enalapril, tended to increase the risk of psoriasis statistically.

KEYWORDS:

• Psoriasis
• angiotensin-converting enzyme inhibitor
• drug safety
• drug-target mendelian randomization
• real-world pharmacovigilance analysis

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions statement

P Song and Q Jin designed the study. Q Jin and F Ren performed the computations and manuscript writing. All authors contributed to the article and approved the submitted version. Q Jin and F Ren contributed equally to this work and share first authorship.

Data availability statement

Summary statistics of diastolic and systolic blood pressure can be downloaded from IEU consortium (https://gwas.mrcieu.ac.uk/). GWAS data on psoriasis is published by Finngen research (https://www.finngen.fi). The pQTL statistics of plasma ACE is publicly available on the Decode database (https://download.decode.is/form/folder/proteomics). Further inquiries can be directed to the corresponding author.

Acknowledgments

We would like to thank the participants and researchers of the FAERS database, IEU OpenGWAS project and FinnGen study. In addition, we want to acknowledge Figdraw (https://www.figdraw.com) for their assistance in Figure 1.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17512433.2023.2292605.

Additional information

Funding

This manuscript was funded by National Natural Science Foundation of China (82074448). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.