Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura.

INTRODUCTION

Idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune hemorrhagic disease characterized by breakdown of self-tolerance and triggering autoreactive lymphocytes' response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays an essential role in maintaining T-cell function, and impaired methylation can lead to inappropriate gene expression and contribute to T-cell autoreactivity and autoimmunity. The aim of this study was to evaluate the role of DNA methyltransferase 3A gene expression in the pathogenesis of ITP.

METHODS

This study included 60 subjects: 20 healthy volunteers as a control group, 20 patients with acute ITP, and 20 patients with chronic ITP. DNA methyltransferase 3A (DNMT3A) mRNA expression in peripheral blood mononuclear cells was measured by real-time quantitative polymerase chain reaction. Plasma S-adenosylhomocysteine (SAH) levels were assayed with reversed-phase high-performance liquid chromatography.

RESULTS

DNMT3A mRNA expression was significantly decreased in patients with ITP as compared with that of the control group. Plasma SAH level was significantly elevated in patients with ITP than in healthy controls. However, no significant difference was found in DNMT3A mRNA expression or plasma SAH level between patients with acute and chronic ITP.

CONCLUSIONS

Aberrant DNA methylation status reflected by decreased mRNA expression of DNMT3A and increased plasma SAH level may play an important role in the pathogenesis of ITP, although the precise underlying mechanisms still await further investigations, and extensive work in this field is clearly needed to provide novel therapeutic targets for ITP.