Background: Although juvenile idiopathic arthritis (JIA) is one of the most common pediatric rheumatologic diseases, the exact etiology of JIA remains unclear. Genetic factors, including variations in the NLRP3 gene, have been implicated in the pathogenesis of autoimmune diseases. Therefore, we aimed to investigate the association between NLRP3 polymorphisms and JIA.
Material and method: We conducted a case-control study involving 51 JIA patients and 56 healthy controls from the Children's Medical Center Hospital. Genotyping of four NLRP3 single nucleotide polymorphisms (SNPs) (rs10754558, rs3806265, rs4612666, and rs35829419) was performed using real-time polymerase chain reaction (PCR). Statistical analysis was conducted to compare allele and genotype frequencies between cases and controls. Additionally, haplotype analysis and evaluation of information interaction between SNPs were performed.
Results: Allele and genotype frequencies of the investigated NLRP3 SNPs did not show significant differences between JIA cases and healthy controls. However, a notable difference in information interaction was observed at the rs4612666/rs3806265 SNPs (p-value = 0.000426). The CCCT haplotype was associated with increased odds of JIA with an odds ratio (OR) of 2.166 (95%CI:1.156-4.06), and contrariwise, the TCGT haplotype was associated with lower odds of JIA with an OR of 0.166 (95%CI:0.036-0.763).
Results: The NLRP3 gene could be involved in the pathogenesis of JIA. Further research with larger cohorts and functional studies is warranted to confirm these findings and elucidate the underlying biological mechanisms. Key Points • No significant difference was observed in the allelic and genotype distribution of NLRP3 SNPs (rs10754558, rs3806265, rs4612666, and rs35829419) between JIA cases and the control group. • A statistically significant difference in information interaction between cases and the control group was observed in rs4612666/rs3806265 SNPs. • The CCCT haplotype was associated with a higher risk of JIA, while the TCGT haplotype was associated with a lower risk.
Keywords: Inflammasome; Juvenile idiopathic arthritis; NLRP3; Polymorphism; Single-nucleotide polymorphism.
© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).