The Synergistic Effect of TNFα -308 G/A and TGFβ1 -509 C/T Polymorphisms on Hepatic Fibrosis Progression in Hepatitis C Virus Genotype 4 Patients.
Tumor necrosis factor-alpha (TNFα) and transforming growth factor-beta (TGFβ1) cytokines are highly implicated in liver fibrosis. Polymorphisms in these cytokines affect their expression, secretion, and activity. This study aimed to evaluate the influence of TNFα -308 G/A and TGFβ1 -509 C/T polymorphism on hepatic fibrosis progression in Egyptian patients with hepatitis C virus (HCV) genotype 4. Genotyping of TNFα -308 G/A and TGFβ1 -509 C/T was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 122 subjects (50 healthy controls and 72 HCV patients). Also, serum TNFα and TGFβ1 levels were detected by enzyme-linked immunosorbent assay (ELISA). The genotyping results of early (F0-F1, n = 36) and late (F2-F4, n = 36) HCV fibrosis patients showed that late fibrosis patients had higher TNFα -308 AA genotype and TGFβ1 -509 TT genotype than early fibrosis patients (p = 0.016, 0.028, respectively). Moreover, the TNFα and TGFβ1 serum levels were significantly higher in HCV patients with TNFα A containing genotypes (GA+AA) (p = 0.004) and patients with TGFβ1 T containing genotypes (CT+TT) (p = 0.001), respectively. The combined unfavorable TNFα (GA/AA) and TGFβ1 (CT/TT) genotypes were highly associated with abnormal liver function parameters and were significantly higher in high activity (A2-A3) and late fibrosis (F2-F4) HCV patients (p = 0.023, 0.029). The multivariate analysis results confirmed that the combined TNFα-308 (AA) and TGFβ1 -509 (TT) unfavorable genotypes increased the risk of hepatic fibrosis progression by 6.4-fold than combined favorable genotypes (odds ratio: 6.417, 95% confidence interval [1.490-27.641], p = 0.013). In conclusion, both TNFα -308 G/A and TGFβ1 -509 C/T polymorphisms synergistically influence the hepatic fibrosis progression and can be used as potential biomarkers to predict hepatic disease progression in chronic hepatitis C patients.
1 Department of Microbial Biotechnology, National Research Centre , Giza, Egypt .
Noha G
NG
Bader El Din
1 Department of Microbial Biotechnology, National Research Centre , Giza, Egypt .
Sally
S
Farouk
1 Department of Microbial Biotechnology, National Research Centre , Giza, Egypt .
Reem
R
El-Shenawy
2 Department of Biochemistry, Faculty of Science, Ain Shams University , Cairo, Egypt .
Mostafa M
MM
Elhady
1 Department of Microbial Biotechnology, National Research Centre , Giza, Egypt .
Marwa K
MK
Ibrahim
1 Department of Microbial Biotechnology, National Research Centre , Giza, Egypt .
Reham M
RM
Dawood
2 Department of Biochemistry, Faculty of Science, Ain Shams University , Cairo, Egypt .
Ahmed M
AM
Salem
1 Department of Microbial Biotechnology, National Research Centre , Giza, Egypt .
Mostafa K
MK
El Awady
D000328:Adult; D004534:Egypt; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha
cytokine single nucleotide polymorphisms; hepatitis C virus immune response; liver fibrosis progression