187a9068-b890-46d2-972f-a29b88bb3356
title
Association of  TNF-beta  polymorphism with disease severity among patients infected with hepatitis C virus.
b17a24b6-9d1e-49a7-9391-6a09358ae919
abstract
The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear.  Tumour necrosis factor alpha  ( TNF-alpha ) is alleged to contribute in the pathogenesis of chronic HCV infection. Single nucleotide polymorphism in  TNF-alpha  and -beta genes could influence the outcome of HCV infection. The aim was to study single nucleotide polymorphism in  TNF-alpha  promoter region and  Nco I polymorphisms  in the  TNF-beta  gene in patients with chronic hepatitis C. Fifty-two patients with histologically proven chronic hepatitis, who had raised ALT levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308 promoter variant of  TNF-alpha  was performed by PCR with primers that incorporated an Nco I restriction site. For PCR typing of the  TNF-beta  Nco I restriction fragment length polymorphism, sequence specific primers were used. Polymorphism in the  TNF-alpha  G/G, G/A and A/A allele was not different between HCV patients and healthy controls.  TNF-beta  A/A allele was significantly more common (P = 0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant difference was observed for  TNF-beta  G/A and G/G alleles [corrected]. Nco I  TNF-beta  A/A was strongly associated with  -308 TNF-alpha G/G  (RR of HCV persistence = 4.9), indicating possible linkage between  TNF-beta  A/A and  TNF-alpha  G/G allele. Patients with severe hepatic fibrosis more frequently had the  TNF-beta  A/A allele as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such as single nucleotide polymorphisms in  TNF-beta  (A/A allele), may affect the natural course of HCV infection, in particular, the disease progression. Larger studies including cytokine expression profiles are needed to fully understand the contribution of the polymorphisms described in the pathogenesis of chronic hepatitis C.