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.

Keywords

Gene polymorphisms Rheumatoid arthritis HIF-1α Angiogenesis Inflammation