title: Methylation of suppressor of cytokine signalling 1 gene promoter is associated with acute-on-chronic hepatitis B liver failure.
abstract: Suppressor of cytokine signalling 1 (SOCS1) was demonstrated to play an important negative role in fulminant hepatitis and might be involved in acute-on-chronic hepatitis B liver failure (ACHBLF). This study was therefore to identify the potential role of SOCS1 and its promoter methylation pattern in ACHBLF patients. Sixty ACHBLF patients, 60 chronic hepatitis B (CHB) patients and 30 healthy controls were investigated in this study. We found that expression of SOCS1 mRNA in CHB and ACHBLF patients was significantly higher than that in healthy controls. The serum level of IL-6, IFN-γ and TNF-α was significantly higher in ACHBLF than CHB. Increased serum level of IL-6, IFN-γ and TNF-α was correlated with total bilirubin, ALT, PTA and MELD scores in ACHBLF. The degree of methylation of the SOCS1 in ACHBLF patients (35.0%, 21/60) was significantly higher than that in CHB patients (16.7%, 10/60). Furthermore, methylated group showed lower level of SOCS1, and higher MELD scores and mortality rate when compared with unmethylated group of ACHBLF. These results suggested that SOCS1 might contribute to immune-related liver damage in ACHBLF, and its aberrant methylation may be a key event for the prognosis of ACHBLF.
authors.affiliation: Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Y-C
authors.initials: YC
authors.lastname: Fan
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: L-Y
authors.initials: LY
authors.lastname: Wang
authors.forename: T
authors.initials: T
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: Y-P
authors.initials: YP
authors.lastname: Yin
authors.forename: L-H
authors.initials: LH
authors.lastname: Hu
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: F-K
authors.initials: FK
authors.lastname: Sun
authors.forename: K
authors.initials: K
authors.lastname: Wang
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: DNA methylation; acute-on-chronic liver failure; cytokine; immune-related damage; suppressor of cytokine signalling 1