Abstract
Polymorphisms within NF-κB pathway genes may be linked to hepatitis C virus (HCV) infection susceptibility and outcomes. We investigated the associations between single nucleotide polymorphisms (SNPs) in NF-κB and the susceptibility as well as resolution of HCV infection. A Chinese population, including 1125 uninfected control cases, 558 cases with spontaneous viral clearance and 898 cases with persistent HCV infection, was genotyped for four SNPs (rs11820062, rs230530, rs1056890 and rs3774963) using a TaqMan assay. Our logistic analyses indicate that the subjects carrying RelA rs11820062 A allele had a significantly increased risk of HCV susceptibility (PBonferroni < 0.003125 in a dominant or additive model). In stratified analysis, the increased risk associated with rs11820062 A allele on HCV susceptibility remained in some case subgroups. This study demonstrates that a genetic variant involved in the NF-κB pathway gene (rs11820062 A allele) is associated with an increased HCV susceptibility within a high-risk Chinese population.
Highlights
More than 185 million people are estimated to be chronically infected with hepatitis C virus (HCV)
groups for further analysis: the HCV-uninfected controls (Group A) was considered as the control group when compared with group B + C and group B was considered as the control group when compared to group C
Our results indicated that rs11820062 A allele was independently associated with the risk effects of HCV infection
Summary
More than 185 million people are estimated to be chronically infected with hepatitis C virus (HCV). Over 70% of HCV infected patients who fail to eliminate the virus go on to develop chronic hepatitis C (CHC), cirrhosis and hepatocellular carcinoma[3]. Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) exists in almost all mammalian cell types, and controls the transcription of many target genes by binding κB response elements. Activated, it can influence cell differentiation, apoptosis, inflammation processes and immune response[6]. SNP rs11820062 in RelA is significantly associated with kidney function and chronic kidney disease susceptibility[13], and with susceptibility to schizophrenia and may affect androgen receptor transcription factor (TF) binding[14]. NFκB2 rs1056890 has been related to the development of multiple myeloma and response to bortezomib therapy[17], and related to the inflammatory response among patients with secondary lymphedema following breast cancer surgery[18] as well as other immune-related diseases[19,20]
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