A Common Genetic Background for Psoriasis and Cardiovascular Diseases: A Narrative Review

Abstract

Background and aims: Psoriasis is an immune-mediated disease affecting primarily the skin and joints, but which also has systemic implications. There are assumptions about a common genetic background between psoriasis and cardiovascular diseases. This narrative review aims to provide an overview of the existing data regarding the IL-23 rs2066808, IL-23R rs2201841, IL-17RA rs4819554, and IL-17A rs2275913 polymorphisms and their link to psoriasis and cardiovascular diseases.

Methods: PubMed, Web of Science, Scopus, and "SNPedia" searches were conducted to identify the relevant studies between 2007 and 2025 that investigated the association between psoriasis, cardiovascular diseases, and the IL-23 rs2066808, IL-23R rs2201841, IL-17RA rs4819554, and IL17A rs2275913 polymorphisms.

Results: The existing data are conflicting. The polymorphisms could be implicated in psoriasis onset, disease susceptibility, and treatment response. Some of them are also linked to coronary artery disease. Contradictory data could result from the heterogeneity of the population included in the studies and the laboratory techniques used for polymorphism determination.

Conclusion: The interplay between IL-17, IL-23, and genetic polymorphisms illustrates a complex landscape in psoriasis and its associated comorbidities. More standardized case-control studies are needed to confirm this hypothesis. Moreover, extensive studies in diverse populations would be important to clarify these relationships and the potential implications for treatment and management.

Keywords: IL17; IL23; coronary artery disease; polymorphisms; psoriasis.

Figure 1

Article selection protocol.

Figure 2

(Created in BioRender. Lazar, L. (2025) https://BioRender.com/ln3xljd). Note: The link between psoriasis and atherosclerosis: Psoriasis is triggered by non‐specific danger signals (Triggers) consisting of infections, drugs, physical trauma, alcohol, smoking, and autoantigens that act in an individual with a genetic predisposition for the disease. In the initial stages, a major role is played by DCs, antigen‐presenting cells, that recognize antimicrobial peptides (LL‐Cathelicidin) and self‐DNA released by damaged keratinocytes. The activation of plasmacytoid DC and IFN‐α release lead to dermal DC maturation and the release of TNF‐α, IL‐23, and IL‐12 responsible for Th1, Th17, and Th22 activation, differentiation, and the production of cytokines, namely TNF‐α, IFN‐γ, IL‐17, and IL‐22, that disrupt the keratinocyte function and intensify the inflammation. The TNFα‐IL‐23‐Th17 axis perpetuates inflammation in psoriasis. The keratinocyte activation induced by IL‐17 leads to their proliferation and the release of TNF‐α and CCL20, that chemoattracts T cells that produce more IL‐17. The expression of vascular adhesion factors is higher in psoriasis lesions, and it further enhances the adhesion of inflammatory cells to the endothelial cells, perpetuating the inflammation. The blood flow in psoriatic lesions is altered through the vasodilation of the blood vessels in the papillary dermis. The IL‐17 causes endothelial dysfunction, it mediates the expression of chemokines MCP‐1, MMP‐9, it upregulates the IL‐6 and also the chemokines CCL‐2 and CCL8, thus promoting atherosclerosis. The key cytokines implicated in these processes are the targets for the biological treatments, which could halt the detrimental process. pDC‐ Plasmacytoid DCs, IFN‐α‐Interferon alpha, mDC‐Myeloid DCs, TNF‐α‐Tumor necrosis factor alpha, IL‐12‐ Interleukin‐12, IL‐22‐ Interleukin‐22, IL‐23‐ Interleukin‐23, IL‐17‐ Interleukin‐17, IFN‐γ‐Interferon gamma, CCL‐20‐CC chemokine ligand 20, VAF‐ Vascular adhesion factors, PMN‐Polymorphonuclear neutrophils, MF‐Macrophage, MC‐Mast cells, MCP‐1‐Human monocyte chemoattractant protein‐1, MMP9‐Matrix metalloproteinase‐9, IL‐6‐ Interleukin‐6, CCL2‐C‐C motif ligand 2, CCL8‐C‐C motif ligand 8.