Association of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 polymorphisms with systemic lupus erythematosus disease activity and biomarker levels

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with considerable genetic predisposition. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) is crucial for the innate immunity and implicated in SLE pathogenesis. Accordingly, we conducted a case-control study to find the association of NLRP3 variations with SLE susceptibility and disease activity.Three single nucleotide polymorphisms of NLRP3 (rs3806268, rs4612666, and rs10754558) were genotyped in 400 SLE patients and 400 healthy controls; the patients were further divided into mild-to-moderate or high disease activity subgroup. Serum cytokines, complements, and autoantibodies were also detected.We found that rs4612666 TT genotype conferred a higher risk of severe disease activity with adjusted odds ratio = 2.08, P = .02 and adjusted odds ratio  = 2.34, P = .01 in the codominant and recessive model, respectively. Nevertheless, there was no association between the 3 single nucleotide polymorphisms of NLRP3 gene and SLE susceptibility. In addition, C4 decreased significantly in rs3806268 GG (P < .001) and rs4612666 TT genotype carriers (P = .03). A higher trend of interleukin-1β and interleukin-γ release were identified in rs3806268 AA and rs10754558 CC genotype carriers, respectively.NLRP3 polymorphisms are associated with SLE disease activity and hypocomplementemia. Interleukin-1β and interleukin-γ levels in SLE patients are correlated with NLRP3 variants as well.