PCSK3 Overexpression in Sjögren's Syndrome Patients May Be Regulated by rs4932178 SNP in Its Promoter Region and Correlates with IFN-γ Gene Expression

Andrea Latini; Giada De Benedittis; Serena Colafrancesco; Carlo Perricone; Giuseppe Novelli; Lucia Novelli; Roberta Priori; Cinzia Ciccacci; Paola Borgiani

doi:10.3390/genes14050981

PCSK3 Overexpression in Sjögren's Syndrome Patients May Be Regulated by rs4932178 SNP in Its Promoter Region and Correlates with IFN-γ Gene Expression

Genes (Basel). 2023 Apr 26;14(5):981. doi: 10.3390/genes14050981.

Authors

Affiliations

¹ Department of Biomedicine and Prevention, Genetics Section, University of Rome Tor Vergata, 00133 Rome, Italy.
² Division of Rheumatology, Department of Clinical Internal, Anaesthesiologic and Cardiovascular Sciences, Sapienza University, 00133 Rome, Italy.
³ Rheumatology, Department of Medicine, University of Perugia, Piazzale Giorgio Menghini 1, 06129 Perugia, Italy.
⁴ IRCCS NEUROMED, 86077 Pozzilli, Italy.
⁵ School of Medicine, Department of Pharmacology, University of Nevada, Reno, NV 89557, USA.
⁶ UniCamillus, Saint Camillus International University of Health Sciences, 00131 Rome, Italy.
⁷ AOU Policlinico Umberto 1, 00161 Rome, Italy.

Abstract

Background: The PCSK3 gene encodes for the protease enzyme Furin, which promotes proteolytic maturation of important regulators of the immune response, and also enhances the secretion of interferon-γ (IFN). Several studies have suggested its possible involvement in the pathogenesis of chronic inflammatory diseases.

Methods: We investigated the PCSK3 gene expression level in peripheral blood mononuclear cells isolated from Sjögren's Syndrome (SS) patients and healthy controls and we evaluated a possible correlation with IFN-γ gene expression. Moreover, we also explored the variability of two PCSK3 genetic polymorphisms (rs4932178 and rs4702) to evaluate a possible association between these polymorphisms and the expression levels of this gene.

Results: We observed, by RT-qPCR, that the PCSK3 expression level was significantly higher in SS patients compared to the controls (p = 0.028), and we confirmed a positive correlation between PCSK3 and IFN-γ expression levels (p < 0.001). Moreover, we reported that the variant homozygous genotype of rs4932178 SNP is associated with a higher expression of the PCSK3 gene (p = 0.038) and with the SS susceptibility (p = 0.016).

Conclusions: Our data suggest that Furin could play a role in SS development, also promoting IFN-γ secretion.

Keywords: IFN-γ; PCSK3; Sjögren’s syndrome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Furin* / genetics
Gene Expression
Humans
Interferon-gamma / genetics
Interferon-gamma / metabolism
Leukocytes, Mononuclear / metabolism
Promoter Regions, Genetic
Sjogren's Syndrome*

Substances

Furin
Interferon-gamma
FURIN protein, human

Grants and funding

This research was funded primarily by the MUR-PNRR M4-C2-I1.3 PE6 project PE00000019 Heal Italia, and partially by EU-Horizon-HLTH-2021-ID: 101057100 (UNDINE) to G.N.