Table 1.
Genetic variants (SNPs) associated with NASH and NASH-HCC.
| Pathway | Gen | Polymorphism | Effect |
|---|---|---|---|
| Lipid metabolism | PNPLA3 | rs738409 | Increase severe of NAFLD, NASH, fibrosis, and HCC [64,66,67,83,84] |
| TM6SF2 | rs10401969 (C), rs58542926 (C/T) E167K | Associated with steatosis, NASH, fibrosis/cirrhosis [69,70,82] | |
| Metabolism of phospholipids and triacylglycerols | LPIN1 | rs13412852 C/T | Associated with lipid levels, NASH severity, and hepatic fibrosis in children with NAFLD [87] |
| Lipogenesis | HSD17B13 | rs72613567 | Reduced risk of NASH and progressive liver damage [75,76] |
| Energy metabolism | PPARGC1A | rs8192678 GA/AA | Increased risk of NASH [69,70,71] |
| Insulin resistance | ENPP1 | ENPP1 121Glin | Associated with fibrosis [88] |
| IRS-1 | IRS-1 972Arg | Associated with fibrosis [88] | |
| GCKR | rs780094 and rs1260326, encoding Pro446Leu | Increased serum triglycerides and associated with fibrosis [88] | |
| Transfer of neutral lipids to nascent ApoB | MTP | −493 G/T | Susceptibility for NASH [74] |
| VLDL secretion | APOB | Several | Associated with NAFLD, NASH, fibrosis, and HCC [89] |
| TM6SF2 | rs58542926 C/T | Increase in NAFLD, NASH, and fibrosis [89] | |
| De novo lipogenesis regulation | GCKR | rs780094 A/G | Associated with NAFLD, NASH, and fibrosis [89] |
| KLF6 | rs3750861 G/A | Decrease fibrosis [89] | |
| Fibrosis | AGTR1 | rs3772622 | Associated with steatohepatitis and fibrosis [88] |
| Oxidative stress | GCLC | −129 C/T | Associated with NASH [88] |
| UCP2 | −866 G/A, rs695366 | Reduce the risk of NASH [77,88] | |
| Immune response | TNF | G238A (rs361525), G308A (rs1800629) | Susceptibility for insulin resistance, NAFLD, and NASH [88] |
| IL28B | rs12979860 C/T | Decrease fibrosis [89] | |
| Mitochondrial antioxidant | SOD2 | rs4880 C/T | Increase fibrosis [89] |
| Phosphatidylinositol remodeling | MBOAT7 | rs641738 | Associated with NAFLD, NASH, fibrosis, and HCC [89,90] |
| HSD17B13 | rs72613567 A/T, rs143404524 | Decrease NAFLD, NASH, fibrosis, and HCC [90] | |
| Antioxidant activity | HP | Hp 2-2 genotype | Contribute to NASH development [73] |
| Repairon of the sarcolemmal membrane in skeletal muscle | DYSF | rs17007417 | Associated with NASH-HCC [91] |
Abbreviations: AGTR1, angiotensin II receptor type 1; Apo B, apolipoprotein B; ENPP1, ectoenzyme nucleotide pyrophosphate phosphodiesterase 1; GCLC, glutamate-cysteine ligase subunit catalytic; GCKR, glucokinase regulatory protein; HCC, hepatocellular carcinoma; HP, haptoglobin; HSD17B13, 17b-Hydroxysteroid dehydrogenase 13; IL-28B, interleukin 28B; IRS-1, insulin receptor substrate-1; KLF6, krueppel-like factor 6; MBOAT7, membrane-bound O-acyltransferase domain-containing 7; MTP, microsomal triglyceride transfer protein; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PNPLA3, patatin-like phospholipase domain-containing protein 3; SOD2, superoxide dismutase 2; TM6SF2, transmembrane 6 superfamily member 2; TNF, tumor necrosis factor; UCP2, uncoupling protein 2; VLDL, very low-density lipoprotein.