Table 1.
SNPs associated with NAFLD/NASH-related HCC
| Gene | Variant | Normal protein function and variant mechanism | NAFLD/NASH OR (95% CI) | NAFLD/NASH-related HCC OR (95% CI) |
|---|---|---|---|---|
| PNPLA3 (refs. 15,102,108,109) | rs738409 c.444C>G p.I148M |
WT: regulates lipid droplets in hepatocytes Variant: protein ubiquitination is impaired, resulting in the accumulation of hepatic lipid droplets that promote hepatic steatosis |
OR for the G allele in patients with NASH 2.05 (1.86–2.27) versus healthy controls | OR for the G allele in patients with NAFLD-related HCC 2.26 (1.23–4.14) versus patients with NAFLD alone |
| TM6SF2 (refs. 102,103,110,111) | rs58542926 c.449C>T p.E167K |
WT: regulates liver fat metabolism Variant: associated with upregulation of cholesterol and fatty acid biosynthesis pathways |
OR for the T allele in patients with NASH 1.61 (1.34–1.92) versus healthy controls | OR for the T allele in patients with NAFLD-related HCC 1.92 (1.31–2.81) versus patients with NAFLD alone |
| MBOAT7 (refs. 104,105,112) | rs641738 C>T p.G17E |
WT: participates in the regulation of triglyceride metabolism Variant: associated with increased hepatic triglyceride content and steatosis development |
OR for the T allele 1.18 (1.00–1.40) versus C allele in patients with NASH | OR for the T allele in NAFLD-related HCC 2.10 (1.33–3.31) versus patients with NAFLD alone |
| GCKR 106,107,113 | rs1260326 c.1337C>T p.P446L |
WT: regulates glucokinase activity Variant: modulates insulin resistance and inflammatory markers on interaction with plasma n-3 PUFAs |
OR for the T allele in patients with NASH 1.55 (1.10–2.17) versus healthy controls | OR for the T allele in patients with NASH-related HCC 1.84 (1.23–2.75) versus general population |
Odds ratios (ORs) depict the increased presence of each single-nucleotide polymorphism (SNP) associated with developing nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and NAFLD/NASH-related hepatocellular carcinoma (HCC). Data included for ORs are from different cohorts and therefore are not directly comparable across diseases and variants. PUFAs, polyunsaturated fatty acids; WT, wild type.