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

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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 < 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.

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Acknowledgements

We are grateful to our colleagues and patients for their friendly cooperation and participation in the study.

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Authors and Affiliations

  1. Department of Physical Medicine and Rehabilitation with Rheumatology, University Hospital of Split, Spinčićeva 1, 21000, Split, Croatia

    Ivanka Marinović M.D. PhD, Jure Aljinović MD PhD, Daniela Šošo MD & Ela Škorić MD

  2. Department of Blood Transfusion Tissue Typing Laboratory, University Hospital of Split, Spinčićeva 1, 21000, Split, Croatia

    Esma Čečuk-Jeličić PhD

  3. Department of Rheumatology and Clinical Immunology, University Hospital of Split, Spinčićeva 1, 21000, Split, Croatia

    Dijana Perković MD PhD, Daniela Marasović Krstulović MD PhD &  Dušanka Martinović Kaliterna MD PhD

  4. University of Split School of Medicine, Šoltanska 2, 21000, Split, Croatia

    Dijana Perković MD PhD, Daniela Marasović Krstulović MD PhD &  Dušanka Martinović Kaliterna MD PhD

  5. Department of Health Studies, University of Split, Ruđera Boškovića 35, 21000, Split, Croatia

    Ivanka Marinović M.D. PhD, Esma Čečuk-Jeličić PhD & Jure Aljinović MD PhD

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  1. Ivanka Marinović M.D. PhD
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  2. Esma Čečuk-Jeličić PhD
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Corresponding author

Correspondence to Ivanka Marinović M.D. PhD.

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Conflict of interest

I. Marinović, E. Čečuk-Jeličić, D. Perković, D. Marasović Krstulović, J. Aljinović, D. Šošo, E. Škorić and D. Martinović Kaliterna declare that they have no competing interests.

Ethical approval

This study was approved by the University Hospital Centre Split Ethics Committee, and written informed consent was obtained from all participants. All the procedures were in accordance with the ethical standards established by the 1964 Helsinki declaration and its amendments.

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Marinović, I., Čečuk-Jeličić, E., Perković, D. et al. Association of HLA-DRB1 alleles with rheumatoid arthritis in Split-Dalmatia County in southern Croatia. Wien Klin Wochenschr 134, 463–470 (2022). https://doi.org/10.1007/s00508-022-02010-5

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