TY - JOUR
T1 - Association of amino acid variations in the NS5A and E2-PePHD region of hepatitis C virus 1b with hepatocellular carcinoma
AU - Hung, C. H.
AU - Chen, C. H.
AU - Lee, C. M.
AU - Wu, C. M.
AU - Hu, T. H.
AU - Wang, J. H.
AU - Yen, Y. H.
AU - Lu, S. N.
PY - 2008/1
Y1 - 2008/1
N2 - NS5A and E2 proteins of the hepatitis C virus (HCV) have the potential to repress protein kinase R (PKR) that exerts a tumour suppressor function. We investigated the relationship between amino acid variations in the NS5A-PKR-binding domain and E2-PKR-eIF2α phosphorylation homology domain (PePHD) region and the development of hepatocellular carcinoma (HCC) in chronic HCV-1b patients. In a cross-sectional, hospital-based setting, we compared the amino acid sequences of NS5A-PKR-binding domain and E2-PePHD in the sera of 104 chronic hepatitis, 44 cirrhosis and 96 HCC patients. The nucleotide sequences were inferred by direct sequencing of the amplified HCV products and deduced amino acid were compared with the sequence of HCV-J. By univariate analysis, old age, lower viral load, fewer amino acid substitutions in the NS5A-PKR-binding domain (codons 2209-2274) and the interferon sensitivity-determining region (ISDR; codons 2209-2248), and wild-type amino acid at codon 2209 and codon 2240 was significantly correlated with HCC, whereas substitutions in the E2-PePHD was not. Patients with a mutated-type (≥4) NS5A-ISDR had a lower prevalence of HCC than those with intermediate or wild type (P < 0.05). Based on stepwise logistic regression analysis, age [odds ratio (OR): 1.132, P < 0.001], viral load (OR: 0.305, P < 0.001) and mutated-type ISDR (OR: 0.137, P = 0.001) were independently associated with HCC. In conclusion, NS5A-ISDR variations may play an important role in the development of HCV-related HCC.
AB - NS5A and E2 proteins of the hepatitis C virus (HCV) have the potential to repress protein kinase R (PKR) that exerts a tumour suppressor function. We investigated the relationship between amino acid variations in the NS5A-PKR-binding domain and E2-PKR-eIF2α phosphorylation homology domain (PePHD) region and the development of hepatocellular carcinoma (HCC) in chronic HCV-1b patients. In a cross-sectional, hospital-based setting, we compared the amino acid sequences of NS5A-PKR-binding domain and E2-PePHD in the sera of 104 chronic hepatitis, 44 cirrhosis and 96 HCC patients. The nucleotide sequences were inferred by direct sequencing of the amplified HCV products and deduced amino acid were compared with the sequence of HCV-J. By univariate analysis, old age, lower viral load, fewer amino acid substitutions in the NS5A-PKR-binding domain (codons 2209-2274) and the interferon sensitivity-determining region (ISDR; codons 2209-2248), and wild-type amino acid at codon 2209 and codon 2240 was significantly correlated with HCC, whereas substitutions in the E2-PePHD was not. Patients with a mutated-type (≥4) NS5A-ISDR had a lower prevalence of HCC than those with intermediate or wild type (P < 0.05). Based on stepwise logistic regression analysis, age [odds ratio (OR): 1.132, P < 0.001], viral load (OR: 0.305, P < 0.001) and mutated-type ISDR (OR: 0.137, P = 0.001) were independently associated with HCC. In conclusion, NS5A-ISDR variations may play an important role in the development of HCV-related HCC.
KW - Hepatitis C
KW - Hepatocellular carcinoma
KW - Interferon sensitivity-determining region
KW - NS5A
KW - PKR-eIF2α phosphorylation homology domain
UR - http://www.scopus.com/inward/record.url?scp=36949033130&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2893.2007.00892.x
DO - 10.1111/j.1365-2893.2007.00892.x
M3 - 文章
C2 - 18088246
AN - SCOPUS:36949033130
SN - 1352-0504
VL - 15
SP - 58
EP - 65
JO - Journal of Viral Hepatitis
JF - Journal of Viral Hepatitis
IS - 1
ER -