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

Summary 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