rs17401966

This association study of 6039 European subjects (1020 HCC cases, 5019 controls including prospective cohorts) identified PNPLA3 rs738409 (OR=3.91, p=1.14E-09) and TM6SF2 rs58542926 (OR=1.79, p=0.001) as significant risk variants for hepatocellular carcinoma in alcoholic liver disease patients, with a dose-dependent additive effect. PNPLA3 rs738409 was also associated with HCC developed on non-fibrotic liver (OR=2.19, p=0.007), suggesting a direct carcinogenic role independent of cirrhosis.

Case-control study examining 16 SNPs in four genes of the TGFβ signaling pathway (TGFB1, TGFBR1, TGFBR2, TGFBR3) and their association with HBV-related hepatocellular carcinoma in 347 Chinese HCC patients and 881 controls. rs1805110 T allele showed significant association with HCC (OR=1.21, p=0.034), with stronger effect in males (OR=1.33, p=0.005). Haplotype analysis identified protective (C-C-A-C-G, OR=0.72) and risk (T-C-A-C-G, OR=1.35) haplotypes in TGFBR3.

This case-control study of 330 subjects (154 HBV-related HCC patients, 86 chronic hepatitis B patients, 43 HBV self-limited infections, and 47 controls) examined three IL28B SNPs for association with hepatitis B-related hepatocellular carcinoma. The CC genotype at rs12979860 was protective (91.5% in controls vs 72.9% in CHB, P=0.01; vs 74.7% in HCC, P=0.01), while T allele carriers had increased HCC risk (χ²=4.44, P=0.04). Gene-gene interactions between rs12979860 and rs12980275 showed an OR of 11.79 (P=0.04), indicating IL28B polymorphisms influence HBV infection progression and HCC susceptibility.

This review synthesizes genome-wide association studies (GWAS) identifying host genetic factors affecting hepatitis B virus (HBV) infection outcomes. HBV persistence is predominantly associated with HLA genes (HLA-DP, HLA-DQ, HLA-C with OR 0.46-2.31) and immune-related genes including CFB, NOTCH4, CD40, UBE2L3, TCF19, and EHMT2. HBV persistence and hepatitis B vaccine nonresponse share overlapping genetic bases with HLA variants, while genetic risk factors for advanced liver diseases (cirrhosis, hepatocellular carcinoma) are largely distinct.