Variants in two gene members of the TNF ligand superfamily and hepatitis C virus chronic disease

Abstract

Aim: To assess the possible correlation between single nucleotide polymorphisms (SNPs) of two members of TNF ligand superfamily genes, tumor necrosis factor-α (TNF-α) and lymphotoxin-α (LTA), and HCV chronic disease.

Background: The causes of disease progression from hepatitis C virus (HCV) infection to chronic liver disease still remains unclear. Abnormal production of the cytokines alleged to be contributed to progression of the disease or viral persistence. Regulatory mechanisms that control the production of cytokines including genetic polymorphisms, especially at coding/regulatory regions of genes, may affect expression and secretion of the cytokines.

Methods: In this case-control investigation, 258 individuals with serologically proven chronic HCV infection and 277 healthy controls were studied. Genotyping of rs1799964 variant of TNF-α and rs909253 intronic variant in LTA gene were performed. To confirm the results of genotyping, 10% of the specimens analyzed again by sequencing approach.

Results: In this investigation, a significant association was observed between the TNF-α TC genotype and chronic HCV infection (P = 0.035). Moreover, the frequency of C allele was significantly different between control subjects in comparison with chronic HCV patients (P=0.02). On the other hand, no association was found between LTA gene polymorphism and susceptibility to chronic HCV infection.

Conclusion: These findings indicate that genetic variants like single nucleotide polymorphism in TNF-α rs1799964, could be a host factor associated with susceptibility to HCV chronic infection. However, further large scale investigations are needed to confirm this finding.

Keywords: Cytokine; Hepatitis C; Lymphotoxin-α.; Single nucleotide polymorphism.

Figure 1

A comprehensive interaction network of two studied gene members of the TNF ligand superfamily (depicted in dashed bold format) and other associated genes