Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 14, 2016; 22(34): 7767-7777
Published online Sep 14, 2016. doi: 10.3748/wjg.v22.i34.7767
Tumor necrosis factor-α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients
Noha G Bader El Din, Sally Farouk, Reem El-Shenawy, Marwa K Ibrahim, Reham M Dawood, Mostafa M Elhady, Ahmed M Salem, Naglaa Zayed, Ahmed Khairy, Mostafa K El Awady
Noha G Bader El Din, Sally Farouk, Reem El-Shenawy, Marwa K Ibrahim, Reham M Dawood, Mostafa K El Awady, Department of Microbial Biotechnology, National Research Centre, Dokki, Giza 12622, Egypt
Mostafa M Elhady, Ahmed M Salem, Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
Naglaa Zayed, Ahmed Khairy, Endemic Medicine Department, Faculty of Medicine, Cairo University, Giza 11562, Egypt
Author contributions: Bader El Din NG designed and supervised the experiments, analyzed the data and wrote the article; Farouk S performed the research experiments and analyzed the data; El-Shenawy R, Ibrahim MK and Dawood RM helped in DNA extraction and in collecting and analyzing the data; Elhady MM and Salem AM performed the PCR purification and sequence analysis; Zayed N and Khairy A collected the blood samples and patient records; El Awady MK directed the study and provided financial support.
Institutional review board statement: The study was evaluated, reviewed and approved by the National Research Center Institutional Research Ethics Committee Review Board.
Informed consent statement: Informed consents were obtained from all study subjects before enrollment in the study and collection of blood samples.
Conflict-of-interest statement: None.
Data sharing statement: There are no additional data available in relation to this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Noha G Bader El Din, PhD, Professor of Medical Biotechnology, Department of Microbial Biotechnology, National Research Centre, 33 EL Bohouth Street (Former EL Tahrir Street), Dokki, Giza 12622, Egypt. nbadereldin@yahoo.com
Telephone: +20-2-33371362 Fax: +20-2-33370931
Received: May 15, 2016
Peer-review started: May 17, 2016
First decision: June 20, 2016
Revised: July 5, 2016
Accepted: July 31, 2016
Article in press: August 1, 2016
Published online: September 14, 2016
Abstract
AIM

To investigate the association of tumor necrosis factor alpha (TNFα) -G308A polymorphism with different liver pathological changes in treatment-naïve Egyptian patients infected with hepatitis C virus (HCV) genotype 4.

METHODS

This study included 180 subjects, composed of 120 treatment-naïve chronic HCV patients with different fibrosis grades (F0-F4) and 60 healthy controls. The TNFα -G308A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα -G308A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence.

RESULTS

Current data showed that the TNFα -G308A SNP frequency was significantly different between controls and HCV infected patients (P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients (F2-F4, n = 60) than in early fibrosis patients (F0-F1, n = 60) (P = 0.05, 0.04 respectively). Moreover, the GA or AA genotypes increased the TNFα serum level greater than the GG genotype (P = 0.002). The results showed a clear association between severe liver pathological conditions (inflammation, steatosis and fibrosis) and (GA + AA) genotypes (P = 0.035, 0.03, 0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes (GA + AA) were significantly associated with liver inflammation (OR = 3.776, 95%CI: 1.399-10.194, P = 0.009), severe steatosis (OR = 4.49, 95%CI: 1.441-14.0, P = 0.010) and fibrosis progression (OR = 2.84, 95%CI: 1.080-7.472, P = 0.034). Also, the A allele was an independent risk factor for liver inflammation (P = 0.003), steatosis (P = 0.003) and fibrosis (P = 0.014).

CONCLUSION

TNFα SNP at nucleotide -308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected patients

Keywords: Hepatitis C virus immune response, Tumor necrosis factor alpha, Single nucleotide polymorphisms, Cytokine expression, Liver disease progression

Core tip: Tumor necrosis factor alpha (TNFα) is a proinflammatory and antiviral cytokine that plays a major role in liver injury and initiation of the fibrosis process. We investigated the association of TNFα -G308A polymorphism with liver pathological changes in treatment-naïve Egyptian patients infected with hepatitis C virus (HCV) genotype 4. The results showed that the TNFα A allele produced high circulating TNFα in the body, which induces inflammatory response. The TNFα A allele was an independent risk factor for liver inflammation, steatosis and fibrosis. TNFα -G308A represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected patients.