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HIF-1A gene polymorphisms and its protein level in patients with rheumatoid arthritis: a case–control study

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Abstract

Objectives

The aim of the study was to identify HIF-1A genetic variants and their possible association with HIF-1α, VEGF, KDR, RORc and Foxp3 protein levels, and susceptibility to and severity of RA.

Methods

The HIF-1A gene polymorphisms were genotyped for 587 RA patients and 341 healthy individuals. The HIF-1α, VEGF, KDR, RORc and Foxp3serum levels were evaluated.

Results

Under the codominant model, the frequency of the rs12434438 GG genotype was lower in RA patients than in controls (P = 0.02). Under the recessive model (AA + AG vs GG), the association was also significant (OR 3.32; CI 1.19–9.24; P = 0.02). Overall, rs12434438 A/G and rs1951795 A/C are in almost completed linkage disequilibrium with D′ = 0.96 and r2 = 0.85. The HIF-1A rs1951795 A allele was associated with rheumatoid factor (P = 0.02) and mean value of erythrocyte sedimentation rate (ESR) (P = 0.05). In RA patients with HIF-1A rs12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RA patients with the HIF-1A rs12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RA patients with rs12434439 GG.

Conclusion

The polymorphic HIF-1A rs12434439 GG genotype may play a protective role for RA development.

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Acknowledgements

The technical assistance of Wieslawa Frankowska and Teresa Golaszewska is gratefully acknowledged. We are also grateful to all the RA patients and healthy subjects whose cooperation made this study possible.

Funding

The work was supported by Grant S/13, National Institute of Geriatrics, Rheumatology and Rehabilitation.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland

    Agnieszka Paradowska-Gorycka & Barbara Stypinska

  2. Department of Physiology, Pomeranian Medical University, Szczecin, Poland

    Andrzej Pawlik

  3. Department of General and Experimental Pathology, Warsaw Medical University, Warsaw, Poland

    Ewa Haladyj, Katarzyna Romanowska-Próchnicka & Marzena Olesinska

  4. Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637, Warsaw, Poland

    Katarzyna Romanowska-Próchnicka

Authors
  1. Agnieszka Paradowska-Gorycka
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  2. Barbara Stypinska
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  3. Andrzej Pawlik
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  4. Ewa Haladyj
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  5. Katarzyna Romanowska-Próchnicka
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  6. Marzena Olesinska
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Contributions

APG conceived, designed and performed experiments, analyzed and interpreted data and wrote the first draft of the manuscript. BS performed experiments and statistical analysis. AP contributed to drafting the manuscript. KRP, EH and MO were involved in the classification of patients with rheumatoid arthritis, clinical check of patients and treatment control. All authors read and approved the final version.

Corresponding author

Correspondence to Katarzyna Romanowska-Próchnicka.

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Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Responsible Editor: John Di Battista.

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Paradowska-Gorycka, A., Stypinska, B., Pawlik, A. et al. HIF-1A gene polymorphisms and its protein level in patients with rheumatoid arthritis: a case–control study. Inflamm. Res. 67, 423–433 (2018). https://doi.org/10.1007/s00011-018-1134-y

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  • DOI: https://doi.org/10.1007/s00011-018-1134-y

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