Citation: Purzycka-Bohdan, D.; Nedoszytko, B.; Sobalska-Kwapis, M.; Zablotna, M.; ˙ Zmijewski, M.A.; Wierzbicka, J.; Gle ´ n, J.; Strapagiel, D.; Szczerkowska-Dobosz, A.; Nowicki, R.J. Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis. Int. J. Mol. Sci. 2023, 24, 6061. https://doi.org/ 10.3390/ijms24076061 Academic Editor: Edwin Lephart Received: 3 March 2023 Revised: 19 March 2023 Accepted: 21 March 2023 Published: 23 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). International Journal of Molecular Sciences Article Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis Dorota Purzycka-Bohdan 1, * , Boguslaw Nedoszytko 1,2 , Marta Sobalska-Kwapis 3 , Monika Zablotna 1 , Michal A. ˙ Zmijewski 4 , Justyna Wierzbicka 4 , Jolanta Gle ´ n 1 , Dominik Strapagiel 3 , Aneta Szczerkowska-Dobosz 1 and Roman J. Nowicki 1 1 Departmentof Dermatology, Venereology and Allergology, Medical University of Gdansk, 80-210 Gdansk, Poland 2 Molecular Laboratory, Invicta Fertility and Reproductive Centre, 81-740 Sopot, Poland 3 Biobank Laboratory, Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Lodz, Poland 4 Department of Histology, Medical University of Gdansk, 80-211 Gdansk, Poland * Correspondence: purzycka-bohdan@gumed.edu.pl Abstract: Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development with selected single nucleotide polymorphisms (SNPs) of genes in which protein products play a significant role in the regulation of differentiation and function of Tregs. There were three study groups in our research and each consisted of different unrelated patients and controls: 192 PsO patients and 5605 healthy volunteers in the microarray genotyping group, 150 PsO patients and 173 controls in the ARMS–PCR method group, and 6 PsO patients and 6 healthy volunteers in the expression analysis group. The DNA microarrays analysis (283 SNPs of 57 genes) and ARMS–PCR method (8 SNPs in 7 genes) were used to determine the frequency of occurrence of SNPs in selected genes. The mRNA expression of selected genes was determined in skin samples. There were statistically significant differences in the allele frequencies of four SNPs in three genes (TNF, IL12RB2, and IL12B) between early-onset PsO patients and controls. The lowest p-value was observed for rs3093662 (TNF), and the G allele carriers had a 2.73 times higher risk of developing early-onset PsO. Moreover, the study revealed significant differences in the frequency of SNPs and their influence on PsO development between early- and late-onset PsO. Based on the ARMS–PCR method, the association between some polymorphisms of four genes (IL4, IL10, TGFB1, and STAT3) and the risk of developing PsO was noticed. Psoriatic lesions were characterized with a lower mRNA expression of FOXP3, CTLA4, and IL2, and a higher expression of TNF and IL1A in comparison with unaffected skin. In conclusion, the genetic background associated with properly functioning Tregs seems to play a significant role in PsO pathogenesis and could have diagnostic value. Keywords: psoriasis; T lymphocytes; regulatory T cells; genetics; single nucleotide polymorphisms 1. Introduction Psoriasis (PsO) is a chronic, inflammatory, immune-mediated disease with a prevalence of approximately 2–3% in the general population [1]. The development and course of PsO are associated with complex interplay between genetic, environmental, and immunological factors [2]. The activated T lymphocytes as well as cytokines and the growth factors secreted by them constitute a major component of the inflammatory infiltrate within PsO lesions. In particular, dysfunctional helper T cells (Th1, Th17, Th22, and regulatory T cells) are recognized as relevant triggers in PsO development [3]. Int. J. Mol. Sci. 2023, 24, 6061. https://doi.org/10.3390/ijms24076061 https://www.mdpi.com/journal/ijms