Background
Hepatitis C virus (HCV) infection is one of the most common chronic blood-borne infections in the world. The estimated HCV prevalence was 2.35% in 2010, affecting 160 million individuals, 29 million of whom were in China. One significant characteristic of HCV infection is its high possibility of chronicity, which usually leads to cirrhosis and hepatocellular carcinoma.
The human leukocyte antigen (HLA) genomic region at chromosomal position 6p21 encodes many genes, which are important for immune system. These genes are categorized into three basic groups: class I (HLA-A, -B, and -C), class II (HLA-DR, -DQ, and -DP), and class III. Previous studies have focused on classical class-I and -II regions and showed that polymorphisms in these regions were associated with chronic hepatitis C. There are also some non-classic genes located among those classic regions and genetic functions of those genes are not fully understood yet. For example, TAP (the transporter associated with antigen processing) and LMP (large molecular weight proteasome) are located in the HLA-DP and -DQ interval and encode proteins that are involved in antigen processing and presentation. Our earlier work indentified some genomic variants of TAP and LMP that were associated with chronic hepatitis B and hepatitis C.
Among the genes located in the HLA class-II DQ-DP interval, eight genes are categorized into antigen processing/presentation-related genes, including TAP1, TAP2, LMP2, LMP7, HLA-DMA, HLA-DMB, HLA-DOA, and HLA-DOB.TAP1 and TAP2 encode the two subunits of TAP. During antigen presentation, TAP works with its binding protein TAPBP, which is encoded by tapasin located near the centromere of chromosome 6.LMP2 and LMP7 encode LMP. TAP and LMP transport antigenic peptides from the cytosol into the endoplasmic reticulum in an ATP-dependent manner.HLA-DMA and HLA-DMB encode two chains of DM complex, which is required for the assembly of antigenic peptides with the HLA class-II molecules. DO, a protein complex translated from HLA-DOA and HLA-DOB, negatively regulates the activity of DM.
Very few studies have investigated the influence of variants in these nine genes on HCV infection. Considering the importance of antigen presentation during immune response to HCV as well as what we have observed previously, we hypothesized that genomic variants of these genes may play a role in generating immune responses and contribute to the outcomes of HCV infection. The current study was to reveal any possible association of these nine genes with HCV in a Chinese population of former paid-blood donors.