Interferon-stimulated gene 15 in hepatitis B-related liver diseases.
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.
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|108 Military Central Hospital, Hanoi, Vietnam.|Vietnamese-German Center for Medical Research, Hanoi, Vietnam.
Nghiem Xuan
NX
Hoan
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Vietnamese-German Center for Medical Research, Hanoi, Vietnam.
Hoang
H
Van Tong
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|108 Military Central Hospital, Hanoi, Vietnam.|Vietnamese-German Center for Medical Research, Hanoi, Vietnam.
Dao Phuong
DP
Giang
Vietnamese-German Center for Medical Research, Hanoi, Vietnam.|Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
Nguyen Linh
NL
Toan
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Vietnamese-German Center for Medical Research, Hanoi, Vietnam.
Christian G
CG
Meyer
Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.
C-Thomas
CT
Bock
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Vietnamese-German Center for Medical Research, Hanoi, Vietnam.
Peter G
PG
Kremsner
108 Military Central Hospital, Hanoi, Vietnam.|Vietnamese-German Center for Medical Research, Hanoi, Vietnam.
Le Huu
LH
Song
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Vietnamese-German Center for Medical Research, Hanoi, Vietnam.|Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
Thirumalaisamy P
TP
Velavan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000150:complications / Q000235:genetics*; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006515:Hepatitis B virus / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000097:blood / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014452:Ubiquitins / Q000097:blood / Q000235:genetics*; D055815:Young Adult
D016207:Cytokines; D014452:Ubiquitins; C074034:ISG15 protein, human
HBV infection; ISG15; ISG15 polymorphism; ISGlation; Pathology Section; liver diseases