Three Gene Signature for Predicting the Development of Hepatocellular Carcinoma in Chronically Infected Hepatitis C Virus Patients
El Awady, MK; Khedr, A; Abdelhafez, TH; El-Wakeel, KH; Omran, MH; Omran, D; Abdelrahim, ME; Salem, HF; Bader El Din, NG; Dawood, RM; Abd El Rahman, M; Salama, H; Ibrahim, MK
Date issued:
2016
Publisher:
MARY ANN LIEBERT, INC
Series Info:
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH;Volume: 36 Issue: 12 Pages: 698-705
Type:
Article
Keywords:
IL28B
,
RISK-FACTOR
,
HCV INFECTION
,
VIRAL-HEPATITIS
,
CYTOMEGALOVIRUS-INFECTION
,
LIVER FIBROSIS
,
GENOTYPE 4 PATIENTS
,
SPLICE ACCEPTOR SITE
,
GENOME-WIDE ASSOCIATION
,
INTERFERON-BASED THERAPY
,
HCC
,
HCV
,
liver fibrosis
,
IL28B
,
OAS1
,
LMP7
Abstract:
Hepatitis C virus (HCV) is the leading cause of liver fibrosis and hepatocellular carcinoma (HCC). At present, there is no predictive biomarker for the patients at high risk of developing HCC. In this study, we examined the association between single-nucleotide polymorphisms (SNPs) in 3 innate immunity genes [2-5oligoadenylate synthetase 1 (OAS1) rs10774671, interleukin 28B (IL28B) rs12979860, and low molecular mass polypeptide 7 (LMP-7) at codon 49] besides cytomegalovirus (CMV) coinfection and susceptibility to HCC in genotype 4 (GT4) chronically infected Egyptian patients. SNPs were determined using restriction fragment length polymorphism analysis in DNA from HCC patients (n=34) and compared with either controls (n=70) or patients with early grades of liver fibrosis (n=49). Our results demonstrated that patients bearing the genetic combination consisting of LMP-7 CA/AA [OR 4.75, 95% confidence interval (CI) 1.443-15.631, P=0.007] and IL28B rs12979860 CT/TT (OR 6.00, 95% CI 1.603-22.455, P=0.004) and positive for CMV viremia (OR 3.11, 95% CI 1.151-8.412, P=0.02) were more likely to have HCC. However, OAS1 rs10774671 does not seem to contribute to the development of HCC. Binary regression analysis indicated that HCC risk significantly increases with the presence of each unfavorable genotype (LMP-7 CA/AA, IL28B rs12979860 CT/TT), when accompanied by the existence of CMV coinfection (probability of HCC risk is 0.8 for combined factors versus 0.14, 0.07, and 0.07 for individual factor IL28B, LMP-7, and CMV; respectively). These data suggest that the 2 SNPs and the coinfection in concert have potential in predicting the risk of HCC development in patients infected with HCV GT4.
Description:
Accession Number: WOS:000390408300005
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