Tumor necrosis factor-α -G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients.
OBJECTIVE
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).


CONCLUSIONS
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.
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.
Noha G
NG
Bader El Din
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.
Sally
S
Farouk
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.
Reem
R
El-Shenawy
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.
Marwa K
MK
Ibrahim
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.
Reham M
RM
Dawood
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
MM
Elhady
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.
Ahmed M
AM
Salem
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.
Naglaa
N
Zayed
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.
Ahmed
A
Khairy
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 K
MK
El Awady
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004534:Egypt; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000473:pathology; D006801:Humans; D007249:Inflammation; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha
Cytokine expression; Hepatitis C virus immune response; Liver disease progression; Single nucleotide polymorphisms; Tumor necrosis factor alpha
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