Polymorphisms in the NLRP3 gene and risk of primary gouty arthritis

Abstract

The aim of the present study was to investigate the association between genetic variants in 17 tagSNPs of the NLRP3 gene and the susceptibility to primary gouty arthritis. A genotype-phenotype analysis of 480 primary gout and 480 control patients was performed. Samples from all the patients were collected from The Affiliated Hospital of Medical College (Qingdao, China). Seventeen tagSNPs of the NLRP3 gene were amplified using polymerase chain reaction (PCR) and MassARRAY technology was used for single nucleotide polymorphism (SNP) genotyping. The genetic frequency of rs7512998 was significantly different between the gout and control patients (P<0.05), whereas no significant differences were identified for the remaining SNPs. The 17 SNPs conformed to the Hardy-Weinberg equilibrium (HWE) in the control group (P>0.05). The haplotype association among the 17 SNPs of the NLRP3 gene indicated that no individual SNP was significantly associated with primary gouty arthritis. CTATCAGCGCCCAGTGC was the most common haplotype in the case and control groups, with a frequency of 0.224 and 0.243, respectively. However, the odds ratios (ORs) of the 8 haplotypes were not identified to be significantly associated with gouty arthritis (P>0.05 for all the 8 haplotypes). To the best of our knowledge, this is the first study to investigate the association between SNPs of the NLRP3 gene and the risk of primary gouty arthritis, although no significant association was identified. Further clinical studies and functional analysis are required to explore the potential associations between NLRP3 gene polymorphisms and the risk of primary gouty arthritis.

Investigation on the association between NLRP3 gene polymorphisms and susceptibility to primary gout

“…There are more than 30 single-nucleotide polymorphisms (SNPs) in exon 3 of the NLRP3 gene, and these SNPs encode the nucleotide binding site domain and boundary regions (Aróstegui et al, 2004). Previous studies have reported an association between NALP3 gene polymorphisms and the susceptibility to gout (Miao et al, 2009;Meng et al, 2013), but the results of these studies are inconsistent. In our study, we found no significant difference between NALP3 polymorphisms and primary gout, suggesting that mutations in the NALP3 inflammasome may not be involved in the susceptibility to gouty development.…”

“…Several previous studies have reported the role of NALP3 gene polymorphisms in the development of gout in different ethnicities (Miao et al, 2009;Meng et al, 2013). Meng et al (2013) conducted a study in a Chinese population including 480 cases with primary gouty and 480 control subjects to investigate the association between 17 SNPs in NALP3 and the susceptibility of gouty development.…”

“…Meng et al (2013) conducted a study in a Chinese population including 480 cases with primary gouty and 480 control subjects to investigate the association between 17 SNPs in NALP3 and the susceptibility of gouty development. However, they found no significant association between NLRP3 gene polymorphisms and the risk of primary gouty arthritis.…”

“…The expression of LRR and PYD domains-containing protein 3 (NALP3) is involved in the activation of caspase-1 and the production of IL-1β. Previous studies reported an association between NALP3 gene polymorphisms and the susceptibility to gout, but the results have been inconsistent (Miao et al, 2009;Meng et al, 2013). Therefore, we conducted a case-control study to investigate the association between 3 common NALP3 polymorphisms (rs10754558, rs7512998, and rs12137901) and the susceptibility to primary gout.…”

Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout

“…The T allele of CARD8 rs2043211 (C10X) has been associated with increased risk of gout in Chinese [ 17 ], and rs2149356 in toll-like receptor 4 (TLR4), a receptor functionally implicated in MSU-stimulated inflammation [ 18 ], has also been associated with serum IL-1β levels and the risk of gout in Han Chinese [ 19 ]. However, using a haplotype tagging approach, there is no evidence of association between NLRP3 and gout in Chinese [ 20 ]. 1…”