Characteristic mutations in hepatitis C virus core gene related to the occurrence of hepatocellular carcinoma

Abstract

Chronic hepatitis C virus (HCV) infection often results in hepatocellular carcinoma (HCC). Previous studies have shown that there might be some characteristic mutations in the core region of HCV related to HCC. Thus, we downloaded and analyzed HCV genotype 1b core gene sequences from HCV databases online to identify them. Based on the information of the sequences, 63 from patients with HCC and 188 from non-HCC were enrolled into our analysis. Then, the nucleotides at each position were compared by chi(2)-test between the two groups, and 24 polymorphisms were found to be associated with HCC. Further analysis of these 24 polymorphisms by logistic regression indicated that eight were significantly related to the increased HCC risk: A028C, G209A, C219U/A, U264C, A271C/U, C378U/A, G435A/C, and G481A. Moreover, U303C/A was associated with the decreased HCC risk. These mutations could bring about four amino acid substitutions: K10Q, R70Q, M91L, and G161S. In conclusion, eight characteristic mutations in the HCV-1b core gene related to the occurrence of HCC were identified. The structural and functional alterations of core protein due to these mutations and the relationship with the occurrence of HCC need to be further studied.

Figure 1

Secondary structure of wild‐type (a) and mutant (b) hepatitis C virus (HCV)‐1b core protein predicted by Chou–Fasman analysis with Genetyx. The straight, bent, looped, and zigzag lines represent coil, β‐sheet, α‐helix, and turn structures, respectively. The numbers indicate the amino acid positions. A028C might turn the coil stucture of AA8‐12 into β‐sheet and G209A might turn the coil stucture of AA71 into α‐helix. (The secondary structure of the wild type was predicted based on the following consensus amino acid sequence of 1336 HCV‐1b core, except 70R: MSTNPKPQRKTKRNTNRRPQDVKFPGGGQIVGGVYLLPRRGPRLGVRATRKTSERSQPRGRRQPIPKARRPEGRAWAQPGYPWPLYGNEGMGWAGWLLSPRGSRPSWGPTDPRRRSRNLGKVIDTLTCGFADLMGYIPLVGAPLGGAARALAHGVRVLEDGVNYATGNLPGCSFSIFLLALLSCLTIPASA.)