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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.

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BackgroundThe association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS.MethodAll relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI).ResultsA total of 30 case–control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01–1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations.ConclusionThis meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene–environment and gene–gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.

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