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The NLRP3-interleukin1β (IL1β) signaling pathway is involved in monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether single nucleotide polymorphisms (SNPs) in the NLRP3 gene are associated with susceptibility to gouty arthritis (GA) and whether these SNPs alter the expression of components of the NLRP3-IL1β signaling pathway. The rs10754558, rs4612666, and rs1539019 SNPs were detected in 583 patients with GA and 459 healthy subjects. NLRP3 and IL1β mRNA levels in peripheral blood mononuclear cells (PBMCs) and serum IL1β levels were measured in different genotype carriers, and correlations between the NLRP3 SNPs and NLRP3 mRNA, IL1β mRNA, and serum IL1β levels were investigated. The GG genotype of NLRP3 rs10754558 was found to be significantly associated with patients with GA compared to the healthy control subjects via multivariate logistic regression analysis (adjusted OR = 2.68, P = 0.006). The CGA haplotypes were independently associated with patients with GA compared to the healthy control subjects (adjusted OR = 1.968, P = 0.02). The levels of NLRP3 mRNA, IL1β mRNA, and serum IL1β in the patients with GA were significantly different among the three genotypes of rs10754558 (all P < 0.01). The GG genotype of rs10754558 and the CGA haplotype of rs4612666-C, rs10754558-G, and rs1539019-A are both independent risk factors for primary GA development. The rs10754558 polymorphism might participate in regulating immune and inflammation responses in patients with GA by influencing the expression of components of the NLRP3 inflammasome. Future multicenter studies aimed at replicating these findings in an independent population as well as functional tests will aid in further defining the role of these SNPs in the development of GA. [ABSTRACT FROM AUTHOR]

We undertook this study to determine whether the altered toll-like receptor (TLR)4-nuclear factor κB (NFκB)-interleukin1β (IL1β) signaling in peripheral blood of gout patients could provide insights into the pathogenesis of primary gouty arthritis (GA). TLR4 mRNA, TLR4 and NFκBp65 proteins expression and IL1β production were measured in 52 acute GA (AGA) and 34 non-acute GA (NAGA) male patients and 78 male healthy subjects (HC). NFκBp65 transcriptional activity and IL1β production were measured after TLR4 inhibition with anti-TLR4 antibody in peripheral whole blood from 13 AGA patients. The TLR4, NFκBp65 and IL1β expression was significantly increased in the AGA group than those in the NAGA or HC group ( P < 0.05, respectively), also the levels were higher in the NAGA group comparing with those in the HC group ( P < 0.05, respectively). Furthermore, moderate positive correlations were observed between concentration of uric acid and the TLR4 mRNA level, serum IL1β production ( r = 0.649, 0.616), and strong positive correlation was observed between TLR4 mRNA level and serum IL1β ( r = 0.848) in 52 AGA patients. On the other hand, NFκBp65 level and IL1β production were dramatically reduced after TLR4 blockade with anti-TLR4 antibody in peripheral blood from the AGA patients ( P < 0.05, respectively). TLR4-NFκB-IL1β signaling might play a crucial role in the development of acute inflammation in primary gout patients. [ABSTRACT FROM AUTHOR]