SOCS3 genetic variants and promoter hypermethylation in patients with chronic hepatitis B.
The clinical manifestations of hepatitis B viral infection (HBV) include chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). The contribution of negative regulator suppressor of cytokine signaling-3 (SOCS3) promoter variants in HBV disease and SOCS3 hypermethylation in tumor tissues were investigated. The SOCS3 promoter region was screened for polymorphisms in 878 HBV patients and in 272 healthy individuals. SOCS3 promoter methylation was examined by bisulfite sequencing. SOCS3 mRNA expression was quantified in 37 tumor and adjacent non-tumor liver tissue specimens. The minor allele rs12953258A was associated with increased susceptibility to HBV infection (OR=1.3, 95%CI=1.1-1.6, adjusted P=0.03). The minor allele rs111033850C and rs12953258A were observed in increased frequencies in HCC and LC patients compared to CHB patients (HCC: OR=1.7, 95%CI=1.1-2.9, adjusted P=0.046; LC: OR=1.4, 95%CI=1.1-1.9, adjusted P=0.017, respectively). HBV patients with rs111033850CC major genotype had decreased viral load (P=0.034), whereas the rs12953258AA major genotype contributed towards increased viral load (P=0.029). Tumor tissues revealed increased hypermethylation compared to adjacent non-tumor tissues (OR=5.4; 95%CI= 1.9-17.1; P=0.001). Increased SOCS3 expression was observed in HBV infested tumor tissues than non-HBV related tumor tissues (P=0.0048). SOCS3 promoter hypermethylation was associated with relatively low mRNA expression in tumor tissues (P=0.0023). In conclusion, SOCS3 promoter variants are associated with HBV susceptibility and SOCS3 hypermethylation stimulates HCC development.
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi, Vietnam.|Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
Nghiem Xuan
NX
Hoan
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.|Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
Hoang
H
Van Tong
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi, Vietnam.|Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
Dao Phuong
DP
Giang
Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.|Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
Bui Khac
BK
Cuong
Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.|Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.
Nguyen Linh
NL
Toan
German Center for Infection Research, Department for Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Germany.
Heiner
H
Wedemeyer
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 (VG-CARE), Hanoi, Vietnam.
Peter G
PG
Kremsner
Institute of Clinical Infectious Diseases, 108 Military Central Hospital, Hanoi, Vietnam.|Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.
Le Huu
LH
Song
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.|Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam.|Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam.|Faculty of Medicine, Duy Tan University, Da Nang, Vietnam.
Thirumalaisamy P
TP
Velavan
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006515:Hepatitis B virus / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000150:complications / Q000235:genetics* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics*; D019562:Viral Load; D055815:Young Adult
C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein
HBV infection; SOCS3 methylation; SOCS3 variants; liver diseases