NLRP3 gene polymorphisms and expression in rheumatoid arthritis

Abstract

The present study aimed to investigate the association between the single-nucleotide polymorphisms (SNPs) rs4612666 and rs10754558 in the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) gene and the susceptibility to rheumatoid arthritis (RA) in a Han Chinese population. mRNA expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 were determined in peripheral blood mononuclear cells (PBMCs) and neutrophils using reverse-transcription quantitative PCR. The results demonstrated that the C allele at rs4612666 locus and the G allele at rs10754558 locus were associated with significantly increased risk of RA. A statistical significance was also revealed in the dominant model (CC+CT vs. TT: OR=1.549; 95% CI=1.120-2.144; and GG + GC vs. CC: OR=2.000; 95% CI=1.529-2.616; P<0.05). Additionally, the mRNA expression of NLRP3, ASC and caspase-1 in PBMCs and neutrophils derived from patients with RA were significantly upregulated compared with the controls. Furthermore, the mRNA levels of NLRP3, ASC and caspase-1 in PBMCs and neutrophils from patients with active RA were notably increased compared with patients in remission. NLRP3 expression was positively correlated with the levels of C-reaction protein, erythrocyte sedimentation rate and disease activity score of 28 joint counts. Overall, the current study indicated that the NLRP3 rs4612666 and rs10754558 loci were associated with susceptibility to RA. In addition, the results of the present study demonstrated that the high expression of NLRP3 could serve a critical role in the pathogenesis of RA.

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

“…The NLPR3 rs4612666 polymorphism has already been associated with rheumatoid arthritis ( Cheng et al., 2021 ) and cardiovascular diseases ( Mahendra et al., 2021 ). The IL-1β rs1143634 polymorphism is associated with susceptibility to myocardial infarction ( Fang et al., 2018 ), an aggressive phenotype of breast cancer ( Wang and Yuan, 2022 ), and is a predictive factor for a severe course of chronic periodontitis ( Brodzikowska et al., 2019 ).…”

Role of NLRP3 Inflammasome in Rheumatoid Arthritis

“…Polymorphisms in the NLRP3 gene indirectly reflect the susceptibility, disease severity and treatment effect of RA. Rs4612666, rs10754558, rs10159239, and rs35829419 have been investigated as NLRP3 single nucleotide polymorphisms (SNPs) associated with susceptibility to rheumatoid arthritis, in which rs35829419 and CARD8 rs2043211 mutations are related to disease severity, while rs10159239 and rs4612666 are related to the therapeutic response of RA on anti-TNF ( 12 , 83 – 86 ).…”

NLRP3: Role in ischemia/reperfusion injuries

“…Previous studies have reported association between NLRP3 genetic variants and risk of inflammatory conditions such as rheumatoid arthritis ( 94 ) and inflammatory bowel diseases ( 95 ). However, the exact impacts of these variants on I/R injuries have not been identified yet.…”