The interplay between HLA-B and NLRP3 polymorphisms may be associated with the genetic susceptibility of gout

Abstract

Background: HLA and NLRP3 play an important role in the development of various autoimmune and autoinflammatory diseases. Gout is an autoinflammatory disease associated with multiple genetic and environmental factors. The objective of the present study was to evaluate the interaction and association between genetic polymorphisms of HLA-B and the NLRP3 gene in Mexican patients with gout.

Methods and results: Eighty-one patients with gout were included and compared with 95 healthy subjects. The polymorphisms rs4349859, rs116488202, rs2734583 and rs3099844 (within the HLA-B region) and rs3806268 and rs10754558 of the NLRP3 gene were genotyped using TaqMan probes in a Rotor-Gene device. The interactions were determined using the multifactorial dimensionality reduction (MDR) method, while the associations were determined through logistic regression models. The MDR analysis revealed significant interactions between the rs116488202 and rs10754558 polymorphisms with an entropy value of 4.31% (p < 0.0001). Significant risk associations were observed with rs4349859 and rs116488202 polymorphisms (p < 0.01); however, no significant associations were observed with the polymorphisms of the NLRP3 gene.

Conclusions: The results suggest that HLA-B polymorphisms and their interaction with NLRP3 may contribute to the genetic susceptibility of gout.

Keywords: Epistasis; Genetic polymorphisms; Gout; HLA-B; NLRP3.