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

Abstract

AIMTo 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.METHODSThis 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.RESULTSCurrent 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).CONCLUSIONTNFα 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

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Expression of microRNAs-21 and-223 in hepatocellular carcinoma in hepatitis C virus infected Egyptian population

“…Our results agree with other studies reported decreased miR-223 expression in HCC. Khairy et al reported significant decrease in expression level in HCC group compared to non HCC groups (Khairy et al, 2016). Shi et al mentioned that miR-223 down regulated in HCC samples compared to matched non-tumor liver tissue (Shi et al, 2015).…”

“…techniques, including ultrasonography, Computed Tomography (CT) and Magnetic Resonance (MRI), have potentially limiting factors, including their availability, costs, and reproducibility (Khairy et al, 2016). Thus, early detection of HCC is still challenging and requires novel, sensitive and specific biomarkers that could detect tumor at an early stage where curative therapy can be applied (Sakamoto et al, 2010).…”

“…Recent studies have reported that miRNAs regulate a variety of biological processes, including cell proliferation, differentiation and apoptosis (Huang et al, 2015). In addition, altered expression of miRNAs including miR -21 and miR-223 has been linked to the development of different human cancer but their role in HCC remains unclear (Khairy et al, 2016).…”

“…HCC is one of the most common neoplastic disorders worldwide (Forner and Bruix, 2012). In Egypt, it is the second common cancer among men and the sixth common cancer among women and represents the second cause of cancer related death (Bader El Din et al, 2016;Fiorino et al, 2016). It has very poor outcome because it is usually detected in advanced stage due to mild deviation of its clinical and pathological features from chronic liver disease (Sakamoto et al, 2010).…”