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首页> 外文期刊>International journal of immunogenetics >Association of nod‐like receptor protein‐3 single nucleotide gene polymorphisms and expression with the susceptibility to relapsing–remitting multiple sclerosis
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Association of nod‐like receptor protein‐3 single nucleotide gene polymorphisms and expression with the susceptibility to relapsing–remitting multiple sclerosis

机译：NOD样受体蛋白-3单核苷酸基因多态性和表达与复发复杂多发性硬化症的敏感性

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Abstract Nod‐like receptor protein 3 (NLRP3) inflammasome is a multi‐protein complex that controls the production of pro‐inflammatory cytokines, IL‐18 and IL‐1β, through caspase‐1 activation. These inflammatory cytokines play an important role in the development of multiple sclerosis (MS). The inflammasome NLRP3 gene variations and expression level have been suggested to affect the immune system activity. This case–control study was performed to determine the association of NLRP3 genetic variants and differential expression with MS. We analysed four common single nucleotide polymorphisms (SNPs) of NLRP3 (rs‐10754558, rs‐35829419, rs‐3806265, rs‐4612666) in a group of 150 Iranian patients with relapsing–remitting MS (RRMS) in comparison with 100 healthy controls. The genotyping was performed using the TaqMan method. For the analysis of NLRP3 gene expression level, we studied a group of 37 RRMS patients (18 patients at relapse phase and 19 at remission phase, treated with IFN‐β) in comparison with 22 healthy controls using real‐time PCR. In this study, we found that NLRP3 rs3806265 C allele and CC genotype were significantly more frequent in the RRMS patients ( p value?=?0.03 OR?=?1.66, 95% CI?=?1.14–2.43) and p value?=?0.04, OR?=?3.26, 95% CI?=?1.19–8.93, respectively), while the frequency of T allele significantly decreased in controls ( p value?=?0.03, OR?=?0.6, 95% CI?=?0.41–0.87). The frequency of CG genotype at position rs10754558 was also significantly higher in the controls compared with patients ( p value?=?0.03, OR?=?0.5, 95% CI?=?0.30–0.80). Moreover, expression level of the NLRP3 in patients at remission phase was significantly reduced in comparison with patients at relapse phase and also healthy controls ( p ?=?0.01 and p ?=?0.04, respectively). The association of NLRP3 polymorphisms with the susceptibility of MS and its reduced expression after IFN‐β therapy, support the idea that NLRP3 inflammasome could have a critical role in inflammatory responses in MS.
机译：摘要NOD样受体蛋白3（NLRP3）炎症是一种多蛋白质复合物，可通过Caspase -1活化来控制促炎细胞因子，IL-18和IL-1β的产生。这些炎性细胞因子在多发性硬化症（MS）的发育中起着重要作用。已经提出了炎症NLRP3基因变异和表达水平影响免疫系统活性。进行这种情况对照研究以确定NLRP3遗传变体和差异表达与MS的差异。我们分析了NLRP3的四种常见单核苷酸多态性（SNPS）（RS-10754558，RS-35829419，RS-3806265，RS-3806265，RS-4612666，RS-4612666，与100个健康对照相比。使用Taqman方法进行基因分型。对于NLRP3基因表达水平的分析，我们研究了一组37名RRMS患者（18名复发阶段患者，缓解阶段19例，用IFN-β处理）与使用实时PCR的22例健康对照相比。在这项研究中，我们发现RRMS患者中NLRP3 RS3806265 C等位基因和CC基因型在rRMS患者中经常频繁更频繁（p值？= 0.03或α=？1.66,95％ci？=？1.14-2.43）和p值？= ？0.04，或？= 3.26,95％CI？=？1.19-8.93分别），控制等位基因的频率显着降低（P值？= 0.03，或？0.6,95％CI？ =？0.41-0.87）。与患者相比，对照组的CG基因型的频率也显着较高（P值？=Δ= 0.03，或？0.5,95％CI？= 0.30-0.80）。此外，与复发阶段的患者和健康对照相比，缓解阶段的患者NLRP3的表达水平显着降低（P？= 0.01和P？= 0.04）。 NLRP3多态性与MS的易感性及其在IFN-β治疗后的表达减少的关系，支持NLRP3炎症组可能在MS中炎症反应中具有关键作用。

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