Khanmohammadi Shaghayegh, Habibzadeh Amirhossein, Fallahtafti Parisa, Rezaei Arezou, Sadr Maryam, Ziaee Vahid, Rezaei Nima
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, 62 Qarib St., Keshavarz Blvd., Tehran, 14194, Iran.
Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Clin Rheumatol. 2025 Jan;44(1):403-411. doi: 10.1007/s10067-024-07270-2. Epub 2024 Dec 14.
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.
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.
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).
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.
尽管幼年特发性关节炎（JIA）是最常见的儿童风湿性疾病之一，但其确切病因仍不清楚。包括NLRP3基因变异在内的遗传因素已被认为与自身免疫性疾病的发病机制有关。因此，我们旨在研究NLRP3基因多态性与JIA之间的关联。
我们进行了一项病例对照研究，纳入了儿童医学中心医院的51例JIA患者和56例健康对照。使用实时聚合酶链反应（PCR）对四个NLRP3单核苷酸多态性（SNP）（rs10754558、rs3806265、rs4612666和rs35829419）进行基因分型。进行统计分析以比较病例组和对照组之间的等位基因和基因型频率。此外，还进行了单倍型分析以及SNP之间信息相互作用的评估。
所研究的NLRP3 SNP的等位基因和基因型频率在JIA病例组和健康对照组之间没有显示出显著差异。然而，在rs4612666/rs3806265 SNP处观察到信息相互作用存在显著差异（p值 = 0.000426）。CCCT单倍型与JIA发病几率增加相关，优势比（OR）为2.166（95%CI：1.156 - 4.06），相反，TCGT单倍型与JIA发病几率降低相关，OR为0.166（95%CI：0.036 - 0.763）。
NLRP3基因可能参与JIA的发病机制。需要进行更大样本队列的进一步研究和功能研究以证实这些发现并阐明潜在的生物学机制。要点：• JIA病例组和对照组之间NLRP3 SNP（rs10754558、rs3806265、rs4612666和rs35829419）的等位基因和基因型分布未观察到显著差异。• 在rs4612666/rs3806265 SNP处观察到病例组和对照组之间信息相互作用存在统计学显著差异。• CCCT单倍型与JIA的较高风险相关，而TCGT单倍型与较低风险相关。
