Next Article in Journal
Role of Lopinavir/Ritonavir in the Treatment of Covid-19: A Review of Current Evidence, Guideline Recommendations, and Perspectives
Previous Article in Journal
Immunomodulation by an Omega-6 Fatty Acid Reduced Mixed Lipid Emulsion in Murine Acute Respiratory Distress Syndrome
Previous Article in Special Issue
Clinical, Radiological, and Laboratory Features of Spinal Cord Involvement in Primary Sjögren’s Syndrome

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis

College of Medical Sciences, University of Rzeszow, al. Kopisto 2A/24, 35-359 Rzeszow, Poland
Department of Rheumatology and Connective Tissue Disease, Medical University of Lublin, al. Raclawickie 1, 20-059 Lublin, Poland
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(7), 2049;
Received: 17 May 2020 / Revised: 24 June 2020 / Accepted: 27 June 2020 / Published: 30 June 2020
Protein citrullination is carried out by peptidylarginine deiminase type 4 (PAD4) enzyme. As a consequence of this process, post-translationally modified proteins are formed that become antigens for anti-citrullinated protein antibodies (ACPA). The study aimed at identifying whether the PADI4 gene is subject to epigenetic regulation through methylation of its promoter region, whether the degree of methylation differs in healthy individuals vs. rheumatoid arthritis (RA) patients and changes in correlation with ACPA, anti-PAD4 and disease activity. A total of 125 RA patients and 30 healthy controls were enrolled. Quantitative real-time methylation-specific PCR was used to analyze the methylation status. ACPA and anti-PAD4 antibodies were determined in serum by enzyme-linked immunosorbent immunoassay. The differences were observed in the degree of PADI4 gene promoter methylation between RA patients and HC, along with an upward trend for the methylation in RA, which was inversely proportional to the disease activity. A weak or modest negative correlation between the degree of PADI4 gene methylation and anti-PAD4, disease activity score (DAS28) and ACPA level has been found. The elevated methylation is associated with lower disease activity, lower levels of ACPA and aPAD4. The methylation degree in this area is growing up during effective treatment and might play a role in the RA pathophysiology and therefore could be a future therapeutic target.
Keywords: rheumatoid arthritis; DNA methylation; epigenetics; PAD4 gene; RA markers rheumatoid arthritis; DNA methylation; epigenetics; PAD4 gene; RA markers
Show Figures

Graphical abstract

MDPI and ACS Style

Kolarz, B.; Ciesla, M.; Dryglewska, M.; Majdan, M. Peptidyl Arginine Deiminase Type 4 Gene Promoter Hypo-Methylation in Rheumatoid Arthritis. J. Clin. Med. 2020, 9, 2049.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Search more from Scilit
Back to TopTop