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IRF 7 gene expression profile and methylation of its promoter region in patients with systemic sclerosis
Author(s) -
Rezaei Ramazan,
Mahmoudi Mahdi,
Gharibdoost Farhad,
Kavosi Hoda,
Dashti Navid,
Imeni Vahideh,
Jamshidi Ahmadreza,
Aslani Saeed,
Mostafaei Shayan,
Vodjgani Mohammad
Publication year - 2017
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13175
Subject(s) - irf7 , dna methylation , methylation , promoter , peripheral blood mononuclear cell , messenger rna , microbiology and biotechnology , pathogenesis , real time polymerase chain reaction , gene expression , biology , gene , immunology , medicine , cancer research , genetics , in vitro
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.