Decreased mRNA expression levels of DNA methyltransferases type 1 and 3A in systemic lupus erythematosus

Abstract

ObjectivesSystemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease characterized by the presence of autoantibodies directed against nuclear antigens and by chronic inflammation. Although the etiology of SLE remains unclear, the influence of environment factors, which is largely reflected by the epigenetic mechanisms, with DNA methylation changes in particular, is generally considered as main players in the pathogenesis of SLE. We studied DNA methyltransferases’ (DNMTs) type 1, 3A and 3B transcript levels in peripheral blood mononuclear cells from patients diagnosed with systemic lupus erythematosus and from the healthy control subjects. Furthermore, the association of DNMT1, DNMT3A, and DNMT3B mRNA levels with gender, age, and major clinical manifestations was analyzed.MethodsPeripheral blood mononuclear cells (PBMCs) were isolated from 32 SLE patients and 40 healthy controls. Reverse transcription and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were used to determine DNMT1, DNMT3A, and DNMT3B mRNA expression levels.ResultsSignificantly lower DNMT1 (p = 0.015543) and DNMT3A (p = 0.003652) transcript levels in SLE patients were observed compared with healthy controls. Nevertheless, the DNMT3B mRNA expression levels were markedly lower compared with DNMT1 and DNMT3A, both in PBMCs from affected patients and those from control subjects. Furthermore, the DNMT1 transcript levels were positively correlated with SLE disease activity index (SLEDAI) (r s = 0.4087, p = 0.020224), while the DNMT3A transcript levels were negatively correlated with patients age (r s = −0.3765, p = 0.03369).ConclusionsOur analyses confirmed the importance of epigenetic alterations in SLE etiology. Moreover, our results suggest that the presence of some clinical manifestations, such as phototosensitivity and arthritis, might be associated with the dysregulation of DNA methyltransferases’ mRNA expression levels.

Epigenetic regulation of placental gene expression in transcriptional subtypes of preeclampsia

“…Interestingly, one of the most significant methylation and expression relationships observed in this cluster involved DNMT3A (one of the DNA methyltransferase enzymes responsible for de novo methylation): a CpG island site (cg05544807) was hypermethylated in the DNMT3A gene body, compared to cluster 1, and demonstrated a negative relationship to expression. While this likely has global implications for the DNA methylation pattern observed in these cluster 3 placentas, decreased expression of DNMT3A has been specifically implicated in immunological-associated disorders [ 67 , 68 ] and abnormal placentation in preeclampsia [ 69 ]. Therefore, this CpG site may serve as a potential target for the epigenetic modulation of pathological gene expression in this PE subtype.…”

DNA methylation 101: what is important to know about DNA methylation and its role in SLE risk and disease heterogeneity

“…Significantly lower DNMT1 and DNMT3A transcript levels in patients with SLE were observed compared with healthy controls. 48 With lower levels of DNMT1, DNA methylation patterns are not completely copied from parent to daughter cells during mitosis, resulting in passive DNA demethylation. DNMT1 is regulated by the mitogen-activated protein kinase/ERK (MAPK/ERK) signalling pathway.…”

Dynamic DNA Methylation Changes ofTbx21andRorcduring Experimental Autoimmune Uveitis in Mice

“…The methylation level of specific autoimmunity-related genes as seen in various autoimmune disorders, including SLE and RA, may be associated with changes in the expression of enzymes regulating DNA methylation such as the DNMTs [ 22 , 40 ]. The mRNA expressions of DNMT1 and DNMT3a were significantly decreased in the peripheral blood mononuclear cells (PBMCs) of SLE patients as compared to healthy subjects [ 41 ]. An aberrant mRNA expression of DNMT1 was also observed in PBMCs from vitiligo patients [ 42 ].…”