Table 1.
Schematic list of the main inherited variations related to the histological hallmarks of NAFLD.
| Variant | Gene | Global MAF | Function | Effect | Impact | Phenotype |
|---|---|---|---|---|---|---|
| rs738409 C > G | PNPLA3 | 0.26 (G) | Lipid remodeling | p.I148M | Loss-of-function | ↑ NAFLD, NASH, fibrosis, HCC |
| rs58542926 C > T | TM6SF2 | 0.07 (T) | VLDL secretion | p.E167K | Loss-of-function | ↑ NAFLD, NASH, fibrosis |
| rs641738 C > T |
TMC4/
MBOAT7 |
0.37 (T) | Lipid remodeling | p.G17E | Loss-of-function | ↑ NAFLD, NASH, fibrosis, HCC |
| rs1260326 C > T | GCKR | 0.29 (T) | Regulation of DNL | p.P446L | Loss-of-function | ↑ NAFLD, NASH, fibrosis |
| rs72613567 T > TA | HSD17B13 | 0.18 (TA) | Lipid remodeling | Truncated protein | Loss-of-function | ↓ NASH, fibrosis, HCC |
| rs4841132 G > A | PPP1R3B | 0.09 (A) | Glycogen synthesis | Non-coding | Gain-of-function | ↓ NAFLD, fibrosis, HCC |
| rs1801278 C > T | IRS1 | 0.05 (T) | Insulin signaling | p.G972R | Loss-of-function | ↑ Fibrosis |
| rs1044498 A > C | ENPP1 | 0.34 (C) | Insulin signaling | p.K121Q | Gain-of-function | ↑ Fibrosis |
| rs2954021 G > A | TRIB1 | 0.45 (A) | Regulation of DNL | Non-coding | Gain-of-function | ↑ NAFLD |
| rs12137855 C > T | LYPLAL1 | 0.16 (T) | Lipid metabolism | Intronic | Loss-of-function | ↑ NAFLD |
| Several | APOB | NA | VLDL secretion | Protein change | Loss-of-function | ↑ NAFLD NASH, fibrosis, HCC |
| Several | MTTP | NA | VLDL secretion | Protein change | Loss-of-function | ↑NAFLD |
| rs236918 G > C | PCSK7 | 0.26 (C) | Membrane transferrin receptor shedding and regulation of circulating lipids | Intronic | Gain-of-function | ↑ NASH, fibrosis |
| Several | PCSK9 | NA | LDL uptake | Protein change | Loss-of-function | No evidence of association with steatosis |
| Several | LIPA | NA | Lipid remodeling | Protein change | LAL deficiency | ↑ NAFLD, NASH, fibrosis |
| rs56225452 G > A | FATP5 | 0.16 (A) | FFAs uptake | Non-coding | Gain-of-function | ↑ NASH, fibrosis |
| rs13412852 C > T | LPIN1 | 0.21 (T) | Lipid metabolism | Intronic | Not Defined | ↓ NASH, fibrosis |
| rs35568725 A > G | PLIN2 | 0.02 (G) | Lipid remodeling | p.S251P | Loss-of-function | ↑ NAFLD, NASH, IR, atherosclerosis |
| rs884164 A > G | PLIN5 | 0.19 (G) | Lipid remodeling | Non-coding | Loss-of-function | ↑ oxidative stress |
| rs17618244 G > A | KLB | 0.15 (A) | FGF19/FGFR4 pathway | p.R728Q | Loss-of-function | ↓ NASH, fibrosis |
| rs4374383 G > A | MERTK | 0.45 (A) | Innate immunity | Intronic | Loss-of-function | ↓ Fibrosis |
| rs3750861 G > A | KLF6 | 0.07 (A) | HSCs activation | Splice variant IVS1-27G | Loss-of-function | ↓ Fibrosis |
| Several | TERT | NA | Telomere maintenance | Protein change | Loss-of-function | ↑ Fibrosis, HCC |
| rs12979860 C > T | IL28B | 0.36 (T) | Innate immunity | Alternative IFNL3/4 transcription |
Loss-of-function | ↓ NASH, Fibrosis |
| rs3480 A > G |
FNDC5 | 0.42 (G) | HSCs activation | Non-coding | Loss-of-function | ↓ Fibrosis |
| rs4880 C > T |
SOD2 | 0.33 (T) | Mitochondrial antioxidant | p.A16V | Loss-of-function | ↑ Fibrosis |
| rs695366 G > A | UCP2 | 0.26 (A) | Mitochondrial lipid metabolism Oxphos | −866 promoter variant | Gain-of-function | ↓ NASH, fibrosis |
| rs2642438 G > A | MARC1 | 0.19 (A) | Mitochondrial detoxification | p.A165T | Loss-of-function | ↓ NAFLD, NASH, fibrosis |
MAF: minor allele frequency.