Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study

Medicina (Kaunas). 2023 Oct 13;59(10):1824. doi: 10.3390/medicina59101824.

Abstract

Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset.

Keywords: early undifferentiated arthritis; rheumatoid arthritis; single-nucleotide polymorphisms.

MeSH terms

  • Anti-Citrullinated Protein Antibodies
  • Arthritis, Rheumatoid* / genetics
  • Autoantibodies
  • Humans
  • Pilot Projects
  • Rheumatoid Factor
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Vascular Endothelial Growth Factor A*

Substances

  • Anti-Citrullinated Protein Antibodies
  • Autoantibodies
  • Rheumatoid Factor
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Vascular Endothelial Growth Factor A
  • PTPN22 protein, human
  • VEGFA protein, human

Grants and funding

This research was funded by AbbVie “Investigator Initiated Study” grant.