Evaluation of DNMT1 gene expression profile and methylation of its promoter region in patients with ankylosing spondylitis. Issue 11 (November 2016) - Aslani, Saeed
Abstract Ankylosing spondylitis (AS) is an autoimmune disease with a chronic inflammatory arthritis. The critical role of methylation in the biology of immunocytes has increasingly been surveyed to discover disease etiology. DNA methyltransferase 1 (DNMT1) is an enzyme, which establishes and regulates patterns of methylated cytosine residues. The aim of the current investigation was to unveil if methylation circumstances of CpG sites inDNMT1 promoter could affect the mRNA expression level of this gene in peripheral blood mononuclear cells (PBMCs) from AS patients. PBMCs were isolated from whole blood of 40 AS patients and 40 healthy individuals. Total RNA and DNA contents of leukocytes were extracted. Afterward, quantitative analysis was carried out by real-time PCR using the SYBR Green PCR Master Mix. Finally, to determine the methylation level, PCR products of bisulfite-treated DNA from patients and controls were sequenced. Compared with healthy controls, expression level ofDNMT1 in AS patients was significantly downregulated. Methylation ofDNMT1 promoter was significantly higher in AS patients in comparison to controls. While a negative correlation between methylation and expression level ofDNMT1 was observed in AS patients, both methylation and expression level ofDNMT1 did not correlate with clinical manifestations. Considering the observation that decreased expression level ofDNMT1 was associated with hypermethylation ofDNMT1 promoter in PBMCs from AS patients, this survey suggests that dysregulation ofDNMT1 expression through altered methylation level of other target genes would probably contribute to AS development.