Agnieszka Paradowska-Gorycka1, Barbara Stypinska1, Andrzej Pawlik2, Ewa Haladyj3, Katarzyna Romanowska-Próchnicka4,5, Marzena Olesinska3. 1. Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. 2. Department of Physiology, Pomeranian Medical University, Szczecin, Poland. 3. Department of General and Experimental Pathology, Warsaw Medical University, Warsaw, Poland. 4. Department of General and Experimental Pathology, Warsaw Medical University, Warsaw, Poland. katarzyna.prochnicka@gmail.com. 5. Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Spartańska 1, 02-637, Warsaw, Poland. katarzyna.prochnicka@gmail.com.
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.
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 RApatients 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 RApatients 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-1Ars1951795 A allele was associated with rheumatoid factor (P = 0.02) and mean value of erythrocyte sedimentation rate (ESR) (P = 0.05). In RApatients with HIF-1Ars12434439 GG genotype, the parameters of disease activity such as DAS-28, VAS score, Larsen score or HAQ score were lower compared to RApatients with the HIF-1Ars12434439 AA genotype. Moreover, we also observed that Foxp3 serum levels were higher, and RORc2 serum levels were lower in RApatients with rs12434439 GG. CONCLUSION: The polymorphic HIF-1Ars12434439 GG genotype may play a protective role for RA development.
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