Genetic risk factors for hepatocellular carcinoma associated with hepatitis C in Yakut males

Objective. To analyze associations between single-nucleotide polymorphisms (SNPs) in some genes located on the X chromosome and risks for hepatocellular carcinoma (HCC) in Yakut males with chronic hepatitis C infection (HCV). Patients and methods. We examined 140 Yakut males with chronic HCV in the stage of liver cirrhosis formation. In 41 of them, chronic hepatitis was complicated by HCC. All patients were tested for SNPs in the genes located on the X chromosome, including TLR7 (rs179008); TLR7 (rs179009); TLR8 (rs3764879); TLR8 (rs3764880); IRAK1 (rs3027898); MECP2 (rs1734791); TAB3 (rs1000129516); ELK1 (rs1000619237); GPC3 (rs2267531). Results. We found no significant differences in the frequencies of specific alleles of genes involved in TLR7 signaling between patients with chronic HCV and patients with HCC. However, there were significant differences in the distribution of variable sites in the rs2267531 locus of the GPC3 gene. The GPC3 gene encodes glypican-3 known as a regulator of cell proliferation and a highly specific HCC tumor marker. GPC3 mutations are inherited as an X-linked recessive trait and only males manifest this condition. The number of C-allele carriers among HCC patients was 1.5 higher than that among HCV patients without HCC. We found that chronic HCV patients carrying the C-allele are 2.7 times more likely to develop HCC than G-allele carriers (p = 0.0095). Conclusion. We found a SNP in the GPC3 gene, which C-allele was associated with an increased risk of HCC in Yakut males with chronic HCV. This genetic marker can be used for personalized prognosis of the disease course and as a predictor of HCC development in patients with liver cirrhosis. Key words: hepatitis C, hepatocellular carcinoma, glypican-3, single-nucleotide polymorphisms, Toll-like receptors, X chromosome, Yakuts