title: Decreased mRNA expression levels of DNA methyltransferases type 1 and 3A in systemic lupus erythematosus.
abstract: OBJECTIVE
  Systemic 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.
  
  
  METHODS
  Peripheral 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.
  
  
  RESULTS
  Significantly 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) (rs= 0.4087, p = 0.020224), while the DNMT3A transcript levels were negatively correlated with patients age (rs= -0.3765, p = 0.03369).
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781, Poznań, Poland. mjnawrocki@ump.edu.pl.
authors.forename: Mariusz J
authors.initials: MJ
authors.lastname: Nawrocki
authors.affiliation: Department of Rheumatology and Internal Diseases, Poznań University of Medical Science, 135/147 28 Czerwca 1956 r. St., 61-545, Poznań, Poland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Majewski
authors.affiliation: Department of Rheumatology and Internal Diseases, Poznań University of Medical Science, 135/147 28 Czerwca 1956 r. St., 61-545, Poznań, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Puszczewicz
authors.affiliation: Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, 6 Święcickiego St., 60-781, Poznań, Poland.
authors.forename: Paweł P
authors.initials: PP
authors.lastname: Jagodziński
mesh_terms: D000328:Adult; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human
keywords: DNA methylation; Epigenetic alterations; SLE