Esmat Rigi Yousefabadi; Zahra Ourang; Farhad Gharibdoost; Seyedeh Tahereh Faezi; Mohammad Saatchi; Delnya Gholami; Emran Esmaeilzadeh; Hamid Reza Khorram Khorshid
Abstract
Background: DNA methylation plays a key role in systemic lupus erythematosus (SLE) by regulating gene expression and impacting immune system functions. In SLE, abnormal DNA methylation patterns can lead to the overexpression of pro-inflammatory genes and downregulation of the regulatory genes, contributing ...
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Background: DNA methylation plays a key role in systemic lupus erythematosus (SLE) by regulating gene expression and impacting immune system functions. In SLE, abnormal DNA methylation patterns can lead to the overexpression of pro-inflammatory genes and downregulation of the regulatory genes, contributing to autoimmunity. This dysregulation can increase susceptibility to SLE. Understanding these methylation changes could help discover new therapeutic strategies for managing SLE.Objective: To evaluate methylation levels of OAS2 and OAS3 in peripheral blood mononuclear cells (PBMCs) in volunteers with SLE were evaluated.Methods: In this case-control study, we collected 207 peripheral blood samples from 102 SLE patients and 105 healthy subjects. After isolating the PBMCs, methylation analysis was performed using the methylation-quantification of endonuclease-resistant DNA (MethyQESD) method.Results: The control group had an average OAS2 methylation percentage of 40.02% ± 24.59%, whereas the SLE group had a significantly lower average of 19.46% ± 21.98%. This finding indicates a significant hypomethylation of OAS2 in the SLE cohort (P<0.001). Additionally, a significant difference was observed in the mean methylation levels of OAS3, with SLE patients exhibiting 14.11% ± 19.50% compared to healthy controls at 25.32% ± 20.82% (P<0.001). Patients with renal damage also showed significantly lower OAS2 methylation levels than SLE individuals without renal damage (P<0.001). Furthermore, a negative connection was found between the OAS2 methylation level and creatinine (r= -0.266, P= 0.007).Conclusion: The pattern of methylation levels observed in OAS2 and OAS3 within PBMCs may provide valuable insights into the mechanisms underlying SLE development.
Mehrdad Nasrollahzadeh Sabet; Navid Nasrabadi; Zahra Jalili; Bahram Pakzad; Saeideh Davar; Naeim Ehtesham; Sima Jafarpour; Meysam Mosallaei; Emran Esmaeilzadeh
Abstract
Background: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation ...
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Background: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA. Objective: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk. Method: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the real‑time polymerase chain reaction high‑resolution melting (HRM) method. Results: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) and rs4612666 and rs10754558 polymorphism (p < 0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P> 0.05). Conclusion: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.
