BackgroundThe toll-like receptor (TLR)4-interleukin1β (IL1β) signaling pathway is involved in the monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether the TLR4 gene rs2149356 SNP is associated with gouty arthritis (GA) susceptibility and whether rs2149356 SNP impacts the TLR4-IL1β signaling pathway molecules expression.Methods and FindingsThe rs2149356 SNP was detected in 459 GA patients and 669 control subjects (containing 459 healthy and 210 hyperuricemic subjects). Peripheral blood mononuclear cells (PBMCs) TLR4 mRNA and serum IL1β were measured in different genotype carriers, and correlations between TLR4 gene SNP and TLR4 mRNA, IL1β were investigated. The frequencies of the genotype and allele were significantly different between the GA and control groups (P<0.01, respectively). The TT genotype was associated with a significantly increased risk of GA (OR = 1.88); this finding was not influenced by making adjustments for the components of possible confounders (adjusted OR = 1.96). TLR4 mRNA and IL1β were significantly increased in the TT genotype from acute GA patients (P<0.05, respectively), and lipids were significantly different among three genotypes in the GA patients (P<0.05, respectively).ConclusionsThe TLR4 gene rs2149356 SNP might be associated with GA susceptibility, and might participate in regulating immune, inflammation and lipid metabolism. Further studies are required to confirm these findings.

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.