Abstract
Background
Psoriasis is an immune-mediated disease with interactions between genetic and environmental factors. An increasing number of studies are demonstrating the importance of microRNAs (miRNAs) in the pathogenesis of psoriasis. miR-146a, a dominant negative regulator of inflammation, has been consistently reported as overexpressed in the skin and peripheral blood mononuclear cells (PBMCs) of patients with psoriasis. Expression and/or function of this miRNA is highly influenced by genetic variations, some of which have already been associated with susceptibility to psoriasis.
Objective
We sought to study the importance of miR-146a in patients with moderate-to-severe psoriasis and to understand the impact of rs57095329 and rs2910164 polymorphisms in a psoriatic Portuguese population.
Methods
miR-146a circulating levels were quantified using molecular biology techniques in 99 patients with moderate-to-severe psoriasis (35 female, 64 male; age 47.4 ± 10.9 years) and 78 healthy individuals (52 female, 26 male; age 42.4 ± 10.1 years). miRNA expression was correlated with clinicopathological features as well as with genetic data such as the presence of human leukocyte antigen (HLA)-C*0602 allele and two miR-146a polymorphisms (rs2910164 and rs57095329).
Results
miR-146a serum levels were 3.7-fold higher in patients with psoriasis than in controls (p < 0.0001, area under the curve [AUC] 0.75; 95% confidence interval [CI] 0.66–0.83). Of note, miR-146a circulating levels positively correlated with Psoriasis Area and Severity Index (p < 0.05) and body surface area (p < 0.05) indexes. No variations in miR-146a levels were observed with rs2910164 and rs57095329 genotypes.
Conclusion
Circulating miR-146a levels were upregulated in patients with psoriasis, especially in those with active disease. To the best of our knowledge, this is the largest study with a homogenous psoriasis population, and our data could shed light on the pathogenesis of psoriasis, paving the way for new avenues for disease treatment.
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Acknowledgements
The authors acknowledge the patients followed at HSA-CHUP. We also acknowledge the nurses from the Dermatology outpatient clinic and Mrs Dina Lopes for collaboration in sample collection and Ms. Maria Rebelo for technical assistance.
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Bárbara Leal, Cláudia Carvalho, Ana Marta Ferreira, Miguel Nogueira, Sandra Brás, Berta M. Silva, Manuela Selores, Paulo P. Costa, and Tiago Torres have no conflicts of interest that are directly relevant to the content of this article.
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Written informed consent was obtained from every participant in the study in accordance with Helsinki Declaration.
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The study was conceived and designed by Bárbara Leal, Cláudia Carvalho, and Tiago Torres. Material preparation and data collection and analysis were performed by Bárbara Leal, Cláudia Carvalho, Ana Marta, Miguel Nogueira, and Sandra Brás. The first draft of the manuscript was written by Bárbara Leal and Cláudia Carvalho. Miguel Nogueira, Berta M. Silva, Manuela Selores, Paulo Pinho e Costa, and Tiago Torres critically revised the manuscript, and the final version was read and approved by all authors.
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Leal, B., Carvalho, C., Ferreira, A.M. et al. Serum Levels of miR-146a in Patients with Psoriasis. Mol Diagn Ther 25, 475–485 (2021). https://doi.org/10.1007/s40291-021-00531-9
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DOI: https://doi.org/10.1007/s40291-021-00531-9