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Irf7 Gene Expression Profile and Methylation of Its Promoter Region in Patients With Systemic Sclerosis Publisher Pubmed



Rezaei R1, 2 ; Mahmoudi M1 ; Gharibdoost F1 ; Kavosi H1 ; Dashti N1, 2 ; Imeni V1 ; Jamshidi A1 ; Aslani S1 ; Mostafaei S1 ; Vodjgani M2
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Authors Affiliations
  1. 1. Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: International Journal of Rheumatic Diseases Published:2017


Abstract

Objective: The aim of the current study was to evaluate if methylation status of CpG sites of interferon regulatory factor 7 (IRF7) promoter in peripheral blood mononuclear cells (PBMCs) of systemic sclerosis (SSc) patients is involved in pathogenesis of the disease. Methods: PBMCs were isolated from whole blood of 50 SSc patients and 30 controls. After the extraction of total RNA and DNA contents from PBMCs, complementary DNA (cDNA) was synthesized. Afterwards, quantitative analysis of IRF7 messenger RNA (mRNA) was conducted by real-time polymerase chain reaction (PCR). To evaluate the methylation status of the promoter region of IRF7 gene, PCR products of bisulfite-treated DNA from SSc patients and controls were sequenced. Results: The mRNA expression of IRF7 in PBMCs from patients compared with controls was significantly upregulated. While limited cutaneous SSc patients expressed the mRNA of IRF7 higher than controls, the diffuse cutaneous SSc group did not demonstrate significantly increased expression in comparison to controls. Insignificant promoter hypomethylation of IRF7 was observed in SSc patients compared with the control group. However, CpG2 hypomethylation was significantly associated with increased SSc risk. Furthermore, overall promoter methylation and mRNA level of IRF7 were significantly correlated with each other. Nonetheless, none of them correlated with Rodnan score of SSc patients. There was significant difference in IRF7 mRNA expression between CpG8 methylated and unmethylated SSc patients. Moreover, the difference of methylation and expression was not significant between anti-nuclear antibody (ANA)-positive and ANA-negative SSc patients. Conclusions: It is suggested that hypomethylation of the IRF7 promoter might play a role in SSc pathogenesis, probably through promoting the IRF7 expression in PBMCs of patients with SSc. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd
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