Association of HLA-DRB1 alleles with rheumatoid arthritis in Split-Dalmatia County in southern Croatia

Wien Klin Wochenschr. 2022 Jun;134(11-12):463-470. doi: 10.1007/s00508-022-02010-5. Epub 2022 Mar 3.

Abstract

Objective: The aim of this study was to investigate the distribution of HLA-DRB1 alleles in patients with rheumatoid arthritis (RA) in the Sinj Region (SR) and the rest of the Split-Dalmatia County (SDC) in Croatia and to determine their relationship with disease severity.

Methods: A total of 74 RA patients and 80 healthy controls from the SR, and 74 RA patients and 80 healthy controls from the rest of the SDC were genotyped using sequence-specific oligonucleotide primed PCR. High-resolution typing of HLA-DRB1*04 alleles was performed using the single specific primed polymerase chain reaction (PCR-SSP) method. Serum anti-CCP, rheumatoid factor, C‑reactive protein, and erythrocyte sedimentation rate were measured in all RA patients, whereas disease activity was assessed by DAS-28 and functional status by the Health Assessment Questionnaire Disability Index.

Results: The HLA-DRB1*04 allele was more frequent in patients with RA from the SR than that in patients from the rest of the SDC (18.2% vs. 9.5%; P = 0.014), whereas the HLA-DRB1*15 allele was more frequent in patients with RA from the rest of the SDC than in patients from the SR (16.2% vs. 7.4%; P = 0.010). Shared epitope (SE) positive patients from the SR had significantly higher serum anti-CCP and RF antibody levels (P = 0.014 and P = 0.004, respectively), higher disease activity (P = 0.043), and worse functional status (P < 0.001), than SE-positive patients from the rest of the SDC.

Conclusion: The observed higher incidence of more severe forms of RA in the SR in comparison to the rest of the SDC might be associated with the higher incidence of HLA-DRB1*04 allele in the SR.

Keywords: Autoantibodies; Croatia; Disease severity; Rheumatoid arthritis; Shared epitope.

MeSH terms

  • Alleles
  • Anti-Citrullinated Protein Antibodies
  • Arthritis, Rheumatoid* / epidemiology
  • Arthritis, Rheumatoid* / genetics
  • Autoantibodies
  • Croatia / epidemiology
  • Epitopes
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DRB1 Chains* / genetics
  • Humans
  • Peptides, Cyclic / genetics
  • Rheumatoid Factor

Substances

  • Anti-Citrullinated Protein Antibodies
  • Autoantibodies
  • Epitopes
  • HLA-DRB1 Chains
  • Peptides, Cyclic
  • Rheumatoid Factor