Assessment of the association between TNIP1 polymorphism with clinical features and risk of systemic lupus erythematosus.

OBJECTIVE: Over the past decades, TNIP1 has been identified as a strong risk locus in multiple genome-wide association studies (GWAS), spanning multiple populations and various autoimmune diseases. TNIP1 is a polyubiquitin-binding protein that works as a physiological inhibitor of NF-κB and maintains immune homeostasis. Some studies have confirmed that TNIP1 is downregulated in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In the current study, for the first time, we evaluated the possible association between rs6889239 polymorphism in the TNIP1 gene with the risk and clinical characteristics of RA and SLE in the Iranian population. METHOD: In this case-control study, 115 patients with RA, 115 patients with SLE, and 115 unrelated healthy subjects were enrolled to estimate rs6889239 genotypes with real-time PCR high resolution melting (HRM) method. RESULTS: Our results demonstrated considerable associations between CC genotype and C allele of rs6889239 with augmented risk of SLE (OR for CC genotype= 2.23; 95%CI [1.175-4.307], OR for C allele= 1.84; 95%CI [1.254-2.720]). However, there was an insignificant association between genotypes and allele frequencies of rs6889239 with the occurrence risk of RA in the population under study (p > 0.05). Additionally, stratification analysis specified that the C allele in rs6889239 was linked with the incidence of renal involvement in SLE patients and lower age of onset in the RA group (p < 0.05). CONCLUSION: These findings propose a significant association between TNIP1 polymorphism and higher risk of SLE and some clinical characteristics of RA and SLE.

Investigation of rs531564 Polymorphism in the Primary MicroRNA-124 Gene in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: Association with Disease Susceptibility and Clinical Characteristics.

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-miR-124 gene with susceptibility and clinical characteristics of RA and SLE in the Iranian population.

IL-38 as an early predictor of the ischemic stroke prognosis.

BACKGROUND: Ischemic stroke is caused by a sudden neurological defect following a vascular occlusion and elicits a local and systemic inflammation in brain tissue. Interleukin-38 is an anti-inflammatory cytokine associated with ischemic and inflammatory diseases. This study was designed to analyze the effect of tPA therapy on interleukin-38 serum level changes and the serum level of IL-38 in the prognosis of ischemic stroke patients in the next three months. METHODS: We enrolled 29 ischemic stroke patients confirmed by a neurologist based on radiologic and clinical manifestation between 2019 September to 2020 February. The patients who had NIHSS more than 6 with no underlying inflammatory diseases were selected for tPA therapy. On admission and 24 h after tPA therapy, the IL-38 serum level was measured by ELISA kit. RESULTS: The results showed that serum levels of IL-38 were significantly increased after tPA therapy (P < 0.001). A remarkable relationship was observed between the modified Rankin Score (mRS) and IL-38 serum changes in response to tPA therapy (P < 0.001). Besides, IL-38 serum changes following tPA were dramatically related to NIHSS at hospitalization (P = 0.007). Also, our analysis posed a positive relation between NIHSS at hospitalization and mRs criteria (P = 0.023). No notable relation has been observed between IL-38 serum levels before and after tPA and mRs (P = 0.601 and P = 0.074, respectively). Furthermore, there was no evidence for the relation between NIHSS at hospitalization and IL-38 levels before and after tPA (P = 0.457 and P = 0.105, respectively). CONCLUSION: The results indicate that tPA could meaningfully increase the IL-38 serum level. Also, a negative correlation has been found between IL-38 serum changes in response to tPA and mRS. Since the lower changes in IL-38 serum level result in a poorer prognosis, we conclude that IL-38 serum changes might be a novel early predictor factor for ischemic stroke prognosis.

Three functional variants in the NLRP3 gene are associated with susceptibility and clinical characteristics of systemic lupus erythematosus.

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.