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A recent narrative review explores the complex interplay between specific genetic polymorphisms in the IL-23 and IL-17 pathways and their potential link to both psoriasis and cardiovascular diseases.1 While psoriasis is primarily known as a skin and joint condition, it’s increasingly recognized as a systemic inflammatory disease with significant implications for cardiovascular health.2 Previous research has illustrated the higher rates of coronary atherosclerosis, myocardial infarction, stroke, and cardiovascular mortality in patients with psoriasis.
Shared Genetic Underpinnings
The review focused on 4 key genetic polymorphisms: IL-23 rs2066808, IL-23R rs2201841, IL-17RA rs4819554, and IL-17A rs2275913. The underlying hypothesis is that variations in these genes, which are crucial for immune system regulation, may contribute to the development or susceptibility of both psoriasis and cardiovascular diseases. The IL-23/IL-17 axis is central to the inflammatory processes in psoriasis, driving keratinocyte hyperproliferation and contributing to the characteristic psoriatic plaques. This same axis is also implicated in the inflammatory mechanisms that underlie atherosclerosis, a primary driver of cardiovascular diseases.
Conflicting Evidence and Methodological Challenges
The literature review consisted of 22 articles from PubMed, Web of Science, Scopus, and “SNPedia,” all published between 2007 and 2025. Despite the theoretical basis for a shared genetic background, the findings from existing studies are conflicting.
- IL-23 and IL-23R Polymorphisms: Some research suggests that polymorphisms like IL-23 rs2066808 and IL-23R rs2201841 are associated with an increased risk of developing psoriasis, and in some cases, with disease severity. IL-23R rs2201841 has also been tentatively linked to Type 2 diabetes mellitus in psoriatic patients. However, other studies found no significant association between these polymorphisms and psoriasis risk or severity. Similarly, the link between these polymorphisms and specific cardiometabolic diseases remains inconsistent, with some studies showing no association with cardiovascular diseases or risk factors.
- IL-17RA and IL-17A Polymorphisms: Evidence for the role of IL-17RA rs4819554 in psoriasis susceptibility is also mixed, with some studies indicating a link and others refuting it. The IL-17A rs2275913 polymorphism has generally not shown a strong association with psoriasis itself, though it might influence disease duration or treatment response in some populations. For cardiovascular diseases, IL-17RA rs4819554 has been linked to cardiovascular mortality, and IL-17A rs2275913 has shown some association with coronary artery disease (CAD), particularly early-onset CAD, although these findings are not consistently replicated across all studies.
There were some limitations in the eligible studies, including heterogeneous study populations, small sample sizes, methodological inconsistencies, and variations in the laboratory techniques used for polymorphism determination.
Clinical Implications & Future Directions
Even with some conflicting evidence, the review underscores the importance of recognizing psoriasis as a systemic inflammatory disease that extends beyond the skin. The potential shared genetic background with cardiovascular diseases highlights the need for a comprehensive approach to patient management. According to the authors, dermatologists and clinicians should be aware that patients with psoriasis, particularly those with severe disease, may have an increased risk of cardiovascular events.
While targeted therapies like biologics that inhibit the IL-23/IL-17 pathway have shown significant efficacy in treating psoriasis, their impact on associated comorbidities is still being fully understood. Some evidence suggests that these therapies may also have beneficial effects on cardiovascular health. To draw more definitive conclusions on the relationship between genetic polymorphisms, psoriasis, and cardiovascular diseases, there is a need for larger, more standardized case-control studies that include diverse patient populations and uniform protocols. Understanding the genetic basis of psoriasis and its associated comorbidities could lead to more personalized, holistic treatment strategies.
References
1. Lazar AL, Romana Vulturar C, Sitar-Tăut AV, et al. A Common Genetic Background for Psoriasis and Cardiovascular Diseases: A Narrative Review. Health Sci Rep. 2025;8(8):e71128. Published 2025 Aug 13. doi:10.1002/hsr2.71128
2. Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: a systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2(2):e000062. Published 2013 Apr 4. doi:10.1161/JAHA.113.000062