NLRP3 gene polymorphisms and expression in rheumatoid arthritis

Area of Science:

• Genetics
• Immunology
• Rheumatology

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
• The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a role in inflammatory processes.

Purpose of the Study:

• To investigate the association between NLRP3 gene single-nucleotide polymorphisms (SNPs) rs4612666 and rs10754558 and RA susceptibility in a Han Chinese population.
• To evaluate the expression levels of NLRP3, ASC, and caspase-1 in RA patients.

Main Methods:

• Case-control study involving a Han Chinese population.
• Genotyping of NLRP3 SNPs rs4612666 and rs10754558 using SNPscan technology.
• Quantification of NLRP3, ASC, and caspase-1 mRNA expression in peripheral blood mononuclear cells (PBMCs) and neutrophils via reverse-transcription quantitative PCR (RT-qPCR).

Main Results:

• The C allele at rs4612666 and the G allele at rs10754558 were significantly associated with increased RA risk.
• mRNA expression of NLRP3, ASC, and caspase-1 was significantly upregulated in RA patients compared to controls.
• Elevated NLRP3, ASC, and caspase-1 mRNA levels were observed in active RA patients versus those in remission.
• NLRP3 expression positively correlated with C-reaction protein, erythrocyte sedimentation rate, and disease activity score (DAS28).

Conclusions:

• NLRP3 gene polymorphisms rs4612666 and rs10754558 are associated with RA susceptibility.
• Upregulated NLRP3 expression contributes to the pathogenesis of rheumatoid arthritis.