Role of HIF1A gene polymorphisms with serum uric acid and HIF-1α levels in monosodium urate crystal-induced arthritis

Abstract

Background: Gouty arthritis is a metabolic disease characterized by the deposition of monosodium urate crystals in the joints, which triggers the release of interleukin-1β (IL-β) by activating the NLRP3 inflammasome. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor involved in IL-β production and as a regulator of NLRP3.

Objectives: The aims were to analyze the association of HIF1A rs11549465, rs11549467, and rs2057482 variants in patients with gouty arthritis, and to evaluate the correlation between urate and HIF-1α levels according to the associated genotypes.

Methods: Cases and controls were genotyped using TaqMan probes, and urate and HIF-1α levels were quantified. Data were analyzed using SPSS v21 software and P-values < 0.05 were considered statistically significant.

Results: Urate and HIF-1α levels were higher in patients than in controls (P < 0.05). Under the three inheritance models (codominant, dominant, and recessive), the AA genotype of the rs11549467 variant was associated with gout risk (OR = 5.74, P = 0.009, OR = 3.33, P = 0.024, and OR = 9.09, P = 0.003, respectively). There were significant differences in the distribution of serum levels of both HIF-1α (P < 0.0001) and urate (P = 0.016) according to the genotypes of the rs11549467 variant.

Conclusion: These results suggest that the HIF1A rs11549467 variant may play a key role in the pathogenesis of gouty arthritis. Key Points • The pathogenesis of gouty arthritis involves the HIF1A gene. • In patients with gout, the AA genotype of the rs11549467 (HIF1A) variant is associated with increased serum levels of urate and HIF-1α. • HIF-1α is involved in the regulation of IL-1β and NLRP3.

Keywords: HIF1A gene; Genetic polymorphisms; Gouty arthritis; Hypoxia inducible factor-1α; Urate.