Interferon-stimulated gene 15 in hepatitis B-related liver diseases

Autor: Christian Meyer, Thirumalaisamy P. Velavan, Nghiem Xuan Hoan, Hoang Van Tong, C.-Thomas Bock, Peter G. Kremsner, Dao Phuong Giang, Nguyen Linh Toan, Le Huu Song
Rok vydání: 2016
Předmět:
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Nghiem Xuan Hoan 1,2,3,* , Hoang Van Tong 1,3,* , Dao Phuong Giang 1,2,3,* , Nguyen Linh Toan 3,4 , Christian G. Meyer 1,3 , C.-Thomas Bock 5 , Peter G. Kremsner 1,3 , Le Huu Song 2,3,** and Thirumalaisamy P. Velavan 1,3,4,** 1 Institute of Tropical Medicine, University of Tubingen, Tubingen, Germany 2 108 Military Central Hospital, Hanoi, Vietnam 3 Vietnamese-German Center for Medical Research, Hanoi, Vietnam 4 Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam 5 Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany * These authors have contributed equally to this work ** Shared senior authors Correspondence to: Thirumalaisamy P. Velavan, email: // Keywords : HBV infection, liver diseases, ISG15, ISG15 polymorphism, ISGlation, Pathology Section Received : June 11, 2016 Accepted : September 05, 2016 Published : September 10, 2016 Abstract This study investigates the association of Interferon-stimulated gene 15 ( ISG15 ) polymorphisms, ISG15 serum levels and expression with HBV-related liver diseases. The ISG15 promoter and the two exons of the gene were screened for polymorphisms in 766 HBV-infected patients and in 223 controls. Soluble ISG15 levels were measured by ELISA. ISG15 mRNA expression was quantified by qRT-PCR in 36 tumor and adjacent non-tumor tissues. The exon 2 allele rs1921A was found associated with decreased progression of HBV-related liver diseases (LC vs. CHB: OR = 0.6, 95%CI = 0.4-0.8, adjusted P = 0.003; HCC vs. CHB: OR = 0.6, 95%CI = 0.4-0.9, adjusted P = 0.005). The rs1921AA genotype was associated with low levels of AST, ALT and total bilirubin, but with high prothrombin levels ( P < 0.05). ISG15 serum levels were higher among HBV patients compared to controls ( P < 0.0001) and positively associated with HBV-related liver diseases, with highest levels among LC patients. ISG15 levels were correlated with HBV-DNA loads ( P = 0.001). In non-tumor tissues from HCC patients, ISG15 mRNA expression was increased in HBV compared to non-HBV infection ( P = 0.016). The ISG15 rs1921 variant and ISG15 expression are associated with HBV-related liver diseases. Taken together, ISG15 appears to be a proviral factor involved in HBV replication and triggering progression of HBV-related liver diseases.
Databáze: OpenAIRE