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

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.