hrvatski

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

The human leukocyte antigen (HLA) is considered to be the most important genetic risk factor for rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease of unknown etiology. HLA-DRB1 alleles encoding the shared epitope - a five amino acid sequence motif in residues 70–74 of the HLA-DRβ chain (HLA-DRB1*01, *04, *10 and *14) are known to be associated with the onset and the severity of the disease. The frequency of HLA-DRB1 genotypes associated with RA varies within different geographical areas. The aim of this study was to evaluate distribution of HLA-DRB1 alleles in patients with RA in Sinj region (SR) and in the rest of Split-Dalmatia County (SDC), as well as to determine the association of HLA- DRB1 alleles with the severity and progression of RA in these patients. We analyzed 74 patients and 80 healthy subjects from SR as well as 74 patients with RA and 80 healthy subjects from the rest of the SDC. Low- resolution HLA-DRB1 genotyping was performed using PCR-SSO (Luminex platform), while high- resolution typing of HLA-DRB1*04 alleles was performed using PCR-SSP. In patients with RA from the SR frequency of HLA-DRB1*04 allele was significantly higher than in patients from the rest of the SDC (18.2% vs. 9.5% ; P=0.014), while HLA-DRB1*15 allele frequency was significantly lower (7.4% vs. 16.2% ; P=0.010). There was no difference in the frequency of HLA-DRB1*01, HLA*10 and HLA*14 alleles between patients (P=0.119, P=0.325, P=0.278, respectively). The frequency of acute phase reactants and rheumatoid factor was higher in shared epitope positive patients from SR compared with the shared epitope positive patients from the rest of the SDC (P=0.014, and P=0.004, respectively). Shared epitope positive patients from SR also showed higher disease activity (P=0.043), more severe degree of functional disability (P<0.001) and more severe radiological damages (P=0.003), compared with the SE-positive patients from the rest of the SDC. These findings indicate that higher incidence of more severe forms of RA in Sinj region could be explained with higher frequency of certain shared epitope HLA-DRB1 alleles ( HLA-DRB1*04) in patients from SR compared to patients from the rest of SDC.

Rheumatoid arthritis ; Prevalence ; Croatia

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