Objective Nod-like receptor pyrin domain containing 3 ( NLRP3) gene encodes an intracellular receptor whose dysregulation in systemic lupus erythematosus (SLE) has been reported in multiple studies. Activation of NLRP3 inflammasome leads to the induction of inflammatory response via cleaving and producing of specific cytokines. In the present study, we assessed the possible association between three functional polymorphisms in this gene and SLE risk in the Iranian population. These variants include two gain of function (rs4612666 and rs10754558) and one loss of function (rs6672995) which are correlated with modulation of expression of NLRP3. Methods A case-control study involving 110 SLE patients and 116 control subjects was undertaken to estimate the frequency of rs4612666, rs10754558, and rs6672995 genotypes using real-time PCR high resolution melting method (HRM). Results Our findings revealed significant associations between GG genotype and G allele of rs10754558 with increased risk of SLE (OR for GG genotype= 2.82; 95%CI [1.45–5.46]/OR for G allele= 1.97; 95%CI [1.36–2.87]). Although, no significant associations were recognized between allele and genotype frequencies of rs4612666 and rs6672995 polymorphisms with SLE risk ( P > 0.05). Also, our analysis revealed that the C allele in rs4612666 and G allele in rs10754558 was correlated with the severity of disease activity (P < 0.001). Moreover, these common variants were associated with lower age of onset and some clinical symptoms in the patient group, such as skin manifestation, neurological symptom and, renal involvement (P < 0.05). Conclusion This study demonstrates a substantial association between NLRP3 polymorphisms with increased risk, clinical symptoms, and the severity of disease activity of SLE.
Background Considering that many recent studies have reported the prevalence of familial multiple sclerosis (FMS), we performed an updated meta-analysis of the worldwide prevalence of FMS by the addition of recent publications. Methods A search in PubMed, Scopus, the ISI Web of Science, and Google Scholar was undertaken up to 20 December 2020. The inclusion criteria were based on the CoCoPop approach (condition, context, and population). Meta-analysis of the qualified studies was conducted by comprehensive meta-analysis ver. 2 software. Results The pooled prevalence of MS in relatives of 16,179 FMS cases was estimated to be 11.8% (95% CI: 10.7–13) based on a random-effects model. The pooled mean age of disease onset in adult probands was calculated to be 28.7 years (95% CI: 27.2 ± 30.2). Regarding 13 studies that reported the data of FMS in pediatrics (n = 877) and adults (n = 6636), the FMS prevalence in pediatrics and adults was 15.5% (95% CI: 13.8–17.4) and 10.8% (95% CI: 8.1–14.2), respectively. The prevalence of FMS in affected males (n = 5243) and females (n = 11,503) was calculated to be 13.7% (95% CI: 10.1–18.2) and 15.4% (95% CI: 10.3–22.4), respectively. The odds ratio of male/female in FMS cases was not statistically significant (OR = 0.9; 95% CI: 0.6–1.2, P = 0.55). Subgroup analysis demonstrated a significant difference in the prevalence of FMS between the geographical areas (P = 0.007). The meta-regression model indicated that the prevalence of FMS is lower with higher latitude and higher MS prevalence (P < 0.001). In contrast, meta-regression based on prevalence day was not statistically significant (P = 0.29). Conclusions The prevalence of FMS is higher in the pediatric group than that of adults, distinct between geographical areas, and diminishes with the increment of MS prevalence and latitude. Also, the symptoms initiate relatively at younger ages in the FMS cases. Interestingly, our analysis unveiled that FMS is not more prevalent in men than women and the risk of MS development in relatives is not higher when the affected proband is male.
MicroRNA-124 (miR-124) is known as an important regulator of the immune system and inflammatory response. Studies have reported that this miRNA is dysregulated in autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A functional analysis demonstrated that rs531564 (C>G) affects the biogenesis of primary microRNA transcript-124 (pri-miR-124) and changes the expression of mature miR-124. In the present study, for the first time, we intended to evaluate the possible association between rs531564 polymorphism with SLE and RA risk. In this case-control study, 110 patients with SLE, 115 patients with RA, and 120 healthy subjects were enrolled to evaluate rs531564 genotypes with real-time polymerase chain reaction (PCR) high resolution melting method. Our findings demonstrated that frequency of GC genotype and G allele were considerably higher in the control group than RA patients, demonstrating that that GC genotype and G allele have a protective effect for healthy individuals (GC vs CC; OR: 0.29; 95%CI [0.12,0.67] and G vs C; OR: 0.42; 95%CI [0.23,0.78]). However, no significant correlation was confirmed between allele and genotype frequencies of rs531564 with SLE risk (p>0.05). However, the G allele in rs531564 polymorphism was associated with serum level of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-dsDNA antibody, C3, C4, and creatinine, and frequency of renal involvements in SLE patients (p<0.05). Moreover, in RA patients, the G was correlated with lower concentration ESR and CRP (p<0.001). Our findings propose a considerable association between rs531564 polymorphism in the pri-miR124 gene with susceptibility and clinical characteristics of RA and SLE in the Iranian population.
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