Table 1.
Summary of gene variants associated with the presence and/or severity of NAFLD
| Gene name | Variant | In NAFLD | In metabolic disorders | In other liver diseases | Effects of the variant |
| PNPLA3 | rs738409 (I148M) | Increase susceptibility to the whole spectrum of NAFLD.[145] | 1. Increase risk of T2DM.[34]2. Reduce risk of T2DM.[146] | A risk loci for ALD,[41] viral hepatitis.[147,148] | 1. Gain of function: overexpression causes hepatic triacylglycerol accumulation.[149]2. Loss of function: reduce the lipidation of VLDL.[150]3. No function: deficiency in mice showed no hepatic steatosis.[151] |
| TM6SF2 | rs58542926 (E167K) | Associated with risk of NAFLD.[46] | 1. Increase risk of T2DM.[34]2. Protect against CVD.[152,153] | Associated with ALD.[41] | Loss of function: favoring lipid accumulation into the liver.[46] |
| GCKR | rs1260326 (P446L) | Associated with predisposition to NAFLD.[31] | Protect against T2DM.[44] | NA | Loss of function: Elevate hepatic glucose uptake and boost lipogenesis by increasing active cytosolic GCK.[12] |
| MBOAT7 | rs641738 (G17E) | Associated with risk of NAFLD.[43] | NA | A risk factor for ALD[41] and viral hepatitis.[154,155] | Reduced expression.[158] |
| HSD17B13 | rs72613567 (TA) | Reduce risk of NASH, but not steatosis.[33] | NA | Protect against advanced ALD.[156–158] | Loss-of-function[33]: result in an unstable and truncated protein with reduced enzymatic activity[159] |
| TCF7L2 | rs7903146 (CT/TT) | Increase risk of NAFLD.[31] | Increase risk of T2DM.[35] | NA | Loss of function in T2DM: associated with beta-cell dysfunction.[35] |
| SREBF-2 | rs133291 (CT/TT)[36] | Predicts incident NAFLD | Predicts risk of T2DM. | NA | Gain of function |
| ADIPOQ | G45T and G276T | Associated with predisposition to develop NAFLD.[37] | Predict risk of T2DM and obesity.[40] | NA | NA |
| SH2B1 | rs7359397[38] | A higher risk of developing NASH | A higher risk of developing obesity | NA | NA |
ALD: alcoholic liver disease (ALD); CVD: cardiovascular disease; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; NA: not applicable; T2DM: type 2 diabetes mellitus; VLDL: very low-density lipoproteins.