Citation: Tawfik, N.Z.; Abdallah, H.Y.; Hassan, R.; Hosny, A.; Ghanem, D.E.; Adel, A.; Atwa, M.A. PSORS1 Locus Genotyping Profile in Psoriasis: A Pilot Case-Control Study. Diagnostics 2022, 12, 1035. https:// doi.org/10.3390/diagnostics12051035 Academic Editor: Yasuhiro Sakai Received: 11 March 2022 Accepted: 18 April 2022 Published: 20 April 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 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/). diagnostics Article PSORS1 Locus Genotyping Profile in Psoriasis: A Pilot Case-Control Study Noha Z. Tawfik 1, *, Hoda Y. Abdallah 2,3 , Ranya Hassan 4 , Alaa Hosny 5 , Dina E. Ghanem 5 , Aya Adel 5 and Mona A. Atwa 1 1 Dermatology, Venereology and Andrology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt; atwamona@gmail.com 2 Medical Genetics Unit, Histology & Cell Biology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt; hoda_ibrahim1@med.suez.edu.eg 3 Center of Excellence in Molecular and Cellular Medicine, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt 4 Clinical Pathology Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt; rania.moustafa@med.suez.edu.eg 5 Ministry of Health, Cairo 11435, Egypt; eng_aliuop@yahoo.com (A.H.); drdinaghanem@gmail.com (D.E.G.); ayadel90@gmail.com (A.A.) * Correspondence: nohazakaria1@gmail.com; Tel.: +20-127-4504926 Abstract: (1) Background: The psoriasis susceptibility 1 (PSORS1) locus, located within the major histocompatibility complex, is one of the main genetic determinants for psoriasis, the genotyping profile for three single-nucleotide polymorphisms (SNPs) comprising the PSORS1 locus: rs1062470 within PSORS1C1/CDSN genes, rs887466 within PSORS1C3 gene, rs10484554 within LOC105375015 gene, were investigated and correlated with psoriasis risk and severity. (2) Methods: This pilot case- controlled study involved 100 psoriatic patients and 100 healthy individuals. We investigated three SNPs and assessed the relative gene expression profile for the PSORS1C1 gene. We then correlated the results with both disease risk and severity. (3) Results: The most significantly associated SNP in PSORS1 locus with psoriasis was rs10484554 with its C/T genotype 5.63 times more likely to develop psoriasis under codominant comparison. Furthermore, C/T and T/T genotypes were 5 times more likely to develop psoriasis. The T allele was 3 times more likely to develop psoriasis under allelic comparison. The relative gene expression of PSORS1C1 for psoriatic patients showed to be under-expressed compared to normal controls. (4) Conclusions: Our study revealed the association of the three studied SNPs with psoriasis risk and severity in an Egyptian cohort, indicating that rs10484554 could be the major key player in the PSORS1 locus. Keywords: psoriasis; PSORS1C3; PSORS1C1/CDSN; LOC105375015; rs1062470; rs887466; rs10484554; single-nucleotide polymorphism 1. Introduction Psoriasis is a common inflammatory skin disease of multifactorial origin that causes significant stress and morbidity [1]. It most often presents with well-demarcated, scaling and erythematous plaques, often at the extensor surfaces of knees and elbows [2]. Until now, the definite etiopathogenesis of psoriasis is not fully understood, however, it is widely regarded as a multifactorial disorder caused by the interaction between inherited suscepti- bility alleles and environmental triggers (e.g., stress, mechanical trauma and streptococcal infections) in combination with skin barrier disruption and immune dysfunction [3,4]. Recent advancements for expanding our understanding of psoriasis pathophysiology and targeted therapies are currently a hot topic in research [5,6]. Familial recurrence is also well documented and disease concordance is higher in monozygotic vs. dizygotic twins [7]. The main genetic determinant for psoriasis is the Diagnostics 2022, 12, 1035. https://doi.org/10.3390/diagnostics12051035 https://www.mdpi.com/journal/diagnostics