The expression of DNMTs is dramatically decreased in peripheral blood mononuclear cells of male patients with juvenile idiopathic arthritis

Ghavidel, Afshin Abdi; Shiari, Reza; Hassan‐Zadeh, Vahideh; Farivar, Shirin

doi:10.1016/j.aller.2019.08.003

Cited by 7 publications

(7 citation statements)

References 27 publications

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Section: Resultsmentioning

confidence: 99%

“…In addition to genetic determinants, DNA methylation has been implicated in the modulation of gene expression, as gene expression correlates negatively with promoter methylation. 13 To identify CpG sites involved in the relationship between CREM methylation and expression, we retrieved the promoter region of CREM from Ensembl (Figure 4A) 17 and detected CpG sites dispersed over five regions (Figure 4A, Table S3). No change in methylation level associated with sex or age was found (Figure S4).…”

Section: Hypomethylation Of the Crem Promoter In Ramentioning

confidence: 99%

“…Furthermore, if CREM is differentially expressed in RA, the exact molecular events contributing to dysregulated CREM expression are incompletely understood. Genetic and epigenetic determinants of gene expression are well characterized, 12,13 but it is unclear whether differential CREM expression in RA can be attributed to CREM variants and CREM methylation. Indeed, no studies to date have examined these possibilities.…”

Section: Introductionmentioning

confidence: 99%

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Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis

Tseng

Lin

et al. 2022

Eur J Clin Investigation

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Background: Genetic and epigenetic factors are strongly associated with the autoimmune disease rheumatoid arthritis (RA). Cyclic AMP response element modulator (CREM), a gene related to immune system regulation, has been implicated in various immune-mediated inflammatory processes, although it remains unknown whether CREM is involved in RA.Methods: This study enrolled 278 RA patients and 262 controls. Three variants [rs12765063, rs17499247, rs1213386] were identified through linkage disequilibrium and expression quantitative trait locus analysis, and CREM transcript abundance was determined by quantitative real-time polymerase chain reaction.The identified variants were genotyped using the TaqMan Allelic Discrimination assay, and CREM promoter methylation was assessed by bisulphite sequencing.Differences between groups and correlations between variables were assessed with Student's t-tests and Pearson's correlation coefficients. Associations between phenotypes and genotypes were evaluated with logistic regression.Results: Rheumatoid arthritis patients exhibited increased CREM expression (p < .0001), which was decreased by methotrexate (p = .0223) and biologics (p = .0001), but could not be attributed to CREM variants. Interestingly, rs17499247 displayed a significant association with serositis (p = .0377), and rs1213386 increased the risk of lymphadenopathy (p = .0398). Furthermore, seven CpG sites showed decreased methylation in RA (p = .0477~ p < .0001).

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Section: Resultsmentioning

confidence: 99%

Section: Hypomethylation Of the Crem Promoter In Ramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis

Tseng

Lin

et al. 2022

Eur J Clin Investigation

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“…Methyl-CpG binding protein 2, the first identified member of MBPs, binds to 5-hydroxymethylcytosine (5 hmC) and 5-methylcytosine (5 mC) residues [27], and Reumatologia 2022; 60/1 acts as a global silencer [28]. Previously we showed that DNA methyltransferases (DNMTs) are downregulated in JIA patients compared to healthy children [29], which can affect the expression of MBPs.…”

Section: Discussionmentioning

confidence: 99%

Association between forkhead box P3 expression level and gender of Iranian juvenile idiopathic arthritis patients

Ghavidel¹,

Farivar²,

Aghamiri³

et al. 2022

Reumatologia

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Objectives: Juvenile idiopathic arthritis (JIA) is a childhood autoimmune rheumatoid disease. Past studies have confirmed that JIA is a complex disease, which means that genes and environmental factors affect the aetiology of the disease. In this study, we analysed the expression of interleukin 32, forkhead box P3 (FOXP3), methyl-CpG binding domain protein 1 (MBD1), and methyl-CpG-binding protein 2 (MECP2) in peripheral blood mononuclear cells of children with JIA in comparison with the expression of those in healthy children. Interleukin 32 is an inflammatory factor, FOXP3 is a transcription factor, and MBD1 and MECP2 are binding proteins that bind to the methylated deoxyribonucleic acid (DNA). Material and methods: We collected blood from JIA patients who had been diagnosed and classified into clinical subtypes by a rheumatologist from the division of paediatric rheumatology. Healthy children, whose clinical and preclinical analysis confirmed they had no disease and just came to the hospital for a check-up or minor surgical procedures were considered as a control group. Age and gender were matched in patients and the control group. Total ribonucleic acid was extracted from blood, and cDNA was synthesized. Eventually, the transcript levels were analysed by quantitative polymerase chain reaction, and statistical analysis was carried out. Results: Statistical analysis of gene expressions in young females affected by JIA demonstrated that MECP2 and FOXP3 were increased significantly (p-value = 0.002 and 0.05, respectively). Interleukin 32 gene expression was also increased (p-value = 0.14), whereas MBD1 gene expression was decreased (p-value = 0.06); however, these changes in the expression of all 4 genes were not significant in young males. Conclusions: Different expression levels of the mentioned genes between affected young females and males result from hormones in both gender and also methotrexate (MTX) drug. Also, the reason affected young females are more prone to JIA than males can be the lower level of FOXP3 expression in healthy females than healthy males.

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“… 62 Ghavidel et al. 63 found expression of DNMT1 and DNMT3a was significantly lower in the patients with JIA than in the healthy control subjects.…”

Section: Epigenetic Modifications In Jiamentioning

confidence: 98%

The role of epigenetics in childhood autoimmune diseases with hematological manifestations

Gkoutsias

Makis

2022

Pediatric Investigation

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Autoimmune diseases with hematological manifestations are often characterized by chronicity and relapses despite treatment, and the underlying pathogenetic mechanisms remain unknown. Epigenetic alterations play a vital role in the deregulation of immune tolerance and the development of autoimmune diseases. In recent years, study of epigenetic mechanisms in both adult and childhood autoimmune disorders has been seeking to explain the pathophysiology of these heterogeneous diseases and to elucidate the interaction between genetic and environmental factors. Various mechanisms, including DNA methylation, histone modifications (chromatin remodeling), and noncoding RNAs (ncRNAs), have been studied extensively in the context of autoimmune diseases. This paper summarizes the epigenetic patterns in some of the most common childhood autoimmune disorders with hematological manifestations, based on epigenetic studies in children with primary immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), and juvenile idiopathic arthritis (JIA). Research findings indicate that methylation changes in genes expressed on T cells, modifications at a variety of histone sites, and alterations in the expression of several ncRNAs are involved in the pathogenesis of these diseases. These mechanisms not only determine the development of these diseases but also affect the severity of the clinical presentation and biochemical markers. Further studies will provide new tools for the prevention and diagnosis of childhood autoimmune disorders, and possible novel treatment options.

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The expression of DNMTs is dramatically decreased in peripheral blood mononuclear cells of male patients with juvenile idiopathic arthritis

Cited by 7 publications

References 27 publications

Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis

Genetic and epigenetic alterations of cyclic AMP response element modulator in rheumatoid arthritis

Association between forkhead box P3 expression level and gender of Iranian juvenile idiopathic arthritis patients

The role of epigenetics in childhood autoimmune diseases with hematological manifestations

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