4.4 Article

NLRP3 gene polymorphisms and expression in rheumatoid arthritis

期刊

出版社

SPANDIDOS PUBL LTD
DOI: 10.3892/etm.2021.10544

关键词

NOD-; LRR- and pyrin domain-containing protein 3; polymorphism; expression; rheumatoid arthritis

资金

  1. Scientific Research Project for Academic and Technical Leaders, Anhui, China [2017H143]
  2. Linkage Projects of Public Welfare Technology Application Research, Anhui, China [1704f0804024]

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The study investigated the association between NLRP3 gene SNPs rs4612666 and rs10754558 in a Han Chinese population with rheumatoid arthritis (RA) susceptibility. The results showed that specific alleles at these loci were associated with increased RA risk, and high levels of NLRP3 expression may play a critical role in the pathogenesis of RA.
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.

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