Tumor necrosis factor-?-G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients

Abstract

AIM To investigate the association of tumor necrosis factor alpha (TNF?)-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 TNF?-G308A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNF? protein was detected by enzyme-linked immunosorbent assay. The influence of different TNF?-G308A genotypes on TNF? 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 TNF?-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 TNF? 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 TNF? 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 TNF? 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.