Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kolarz B

PROVIDER: S-EPMC7408948 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kolarz Bogdan B Ciesla Marek M Dryglewska Magdalena M Majdan Maria M

Journal of clinical medicine 20200630 7

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 <i>PADI4</i> 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 change ...[more]

PMID: 32629762

Similar Datasets

Project description:IntroductionAnti-cyclic citrullinated peptide autoantibodies (anti-CCP) are the most specific serologic marker for rheumatoid arthritis (RA). Genetic polymorphisms in a citrullinating (or deiminating) enzyme, peptidyl arginine deiminase type IV (PADI4) have been reproducibly associated with RA susceptibility in several populations. We investigated whether PADI4 polymorphisms contribute to anti-CCP-negative as well as -positive RA, whether they influence disease severity (erosive joint status), and whether they interact with two major risk factors for RA, Human Leukocyte Antigen-DRB1 (HLA-DRB1) shared epitope (SE) alleles and smoking, depending on anti-CCP and erosive joint status.MethodsAll 2,317 unrelated Korean subjects including 1,313 patients with RA and 1,004 unaffected controls were genotyped for three nonsynonymous (padi4_89, padi4_90, and padi4_92) and one synonymous (padi4_104) single-nucleotide polymorphisms (SNPs) in PADI4 and for HLA-DRB1 by direct DNA sequence analysis. Odds ratios (OR) were calculated by multivariate logistic regression. Interaction was evaluated by attributable proportions (AP), with 95% confidence intervals (CI).ResultsA functional haplotype of the three fully correlated nonsynonymous SNPs in PADI4 was significantly associated with susceptibility to not only anti-CCP-positive (adjusted OR 1.73, 95% CI 1.34 to 2.23) but also -negative RA (adjusted OR 1.75, 95% CI 1.15 to 2.68). A strong association with both non-erosive (adjusted OR 1.62, 95% CI 1.29 to 2.05) and erosive RA (adjusted OR 1.62, 95% CI 1.14 to 2.31) was observed for PADI4 haplotype. Gene-gene interactions between the homozygous RA-risk PADI4 haplotype and SE alleles were significant in both anti-CCP-positive (AP 0.45, 95% CI 0.20 to 0.71) and -negative RA (AP 0.61, 95% CI 0.29 to 0.92). Theses interactions were also observed for both non-erosive (AP 0.48, 95% CI 0.25 to 0.72) and erosive RA (AP 0.46, 95% CI 0.14 to 0.78). In contrast, no interaction was observed between smoking and PADI4 polymorphisms.ConclusionsA haplotype of nonsynonymous SNPs in PADI4 contributes to development of RA regardless of anti-CCP or erosive joint status. The homozygous PADI4 haplotype contribution is affected by gene-gene interactions with HLA-DRB1 SE alleles.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets