Table 2.
Meta-analyses and Prospective Evidence for the Association of Genetic Variants with NAFLD.
| Gene | SNP | Study type | Study population | Notable cohort characteristics | Sample size | Diagnostic modality |
|---|---|---|---|---|---|---|
| ADIPOQ | rs26672941 | Meta-analysis | Multiethnic (primarily Asian) | HB vs PB not reported | 9 retrospective case–control studies 1223 cases/1580 controls | Liver biopsy only in 3/9 studies |
| APOC3 | rs285411642 | Prospective case–control | Chinese | 67% male subjects | 300 cases/300 controls | US |
| rs2854116 and rs285411743 | Meta-analysisa | Multiethnic | 5 HB vs 2 PB controls; 1 study included pediatric subjects; 2 studies did not report gender % | 7 prospective case–control studies 1745 cases/1437 controls | Liver biopsy only in 2/7 studies 1H-MRS or US in others | |
| GCKR | rs78009444 | Meta-analysis | Multiethnic | 5 HB vs 2 PB controls; 1 of the Asian studies examines pediatric subjects | 5 retrospective case–control studies 2090 cases/3003 controls | Liver biopsy only in 3/5 studies |
| MTHFR | rs180113345 | Meta-analysis | Multiethnic | All 8 studies PB controls | 8 retrospective case–control studies 785 cases/1188 controls | Liver biopsy in 4/5 studies, not reported in Chinese and Ukrainian studies |
| rs1810113145 | Meta-analysis | Multiethnic | All 5 studies PB controls | 5 retrospective case–control studies 476 cases/679 controls | Liver biopsy in 3/4 studies, not reported in Ukrainian study | |
| MTTP | rs180059146 | Meta-analysis | Multiethnic | 6 HB vs 5 PB controls | 11 retrospective case–control studies 636 cases/918 controls | Not reported |
| PEMT | rs794647 | Meta-analysis | Multiethnic (primarily Asian) | 4 HB vs 2 PB controls; 1 study included pediatric subjects |
6 retrospective case–control studies 792 cases/2722 controls | Liver biopsy only in 2/6 studies |
| PNPLA3 | rs73840948 | Meta-analysis | Multiethnic | 11 HB vs 5 PB controls; 5 studies included pediatric subjects | 16 retrospective case–control studies 12,677 total | Liver biopsy only in 6/16 studies 1H-MRS, US, or CT in others |
| rs73840949 | Meta-analysis | Asian | 4 HB vs 8 PB controls | 12 retrospective case–control studies 4495 cases/7431 controls | Liver biopsy only in 5/12 studies | |
| rs73840950 | Meta-analysis | Multiethnic | 15 HB vs 8 PB controls | 23 retrospective case–control studies 5826 cases/10,796 controls | Liver biopsy only in10/23 studies | |
| PPARγ | rs1805192 and rs180128251 | Meta-analysisa | Caucasian and Asian | 4 HB vs 4 PB controls | 8 retrospective case–control studies 1697 cases/2427 controls | Liver biopsy in 5/9 studies |
| rs1805192 and rs180128252 | Meta-analysisb | Caucasian and Asian | HB vs PB not reported | 5 retrospective case–control studies 1225 cases/2016 controls | Not reported | |
| SREBF-2 | rs13329153 | Prospective cohort | Italian | 65% male subjects | 48 cases/127 controls | Liver biopsy |
| TM6SF2 | rs5854292654 | Meta-analysis | Multiethnic | 4 HB vs 3 PB vs 1 mixed controls; 1 of the 2 Italian studies in pediatric |
8 retrospective case–control studies 5537 total | Liver biopsy only in 3/8 studies |
| rs5854292655 | Prospective cohort | Multiethnic | Pediatric cohort | 957 total | Liver biopsy only in 11 patients |
This study demonstrated no association with NAFLD.
This study suggested association with NAFLD in the East Asian population, however not in the European population. ADIPOQ, Adiponectin; APOC3, Apolipoprotein C-III; CT, Computed Tomography; GCKR, Glucokinase Regulator; 1H-MRS, Proton Magnetic Resonance Spectroscopy; HB, Hospital-Based Controls; MTHFR, Methylenetetrahydrofolate REDUCTASE; MTTP, Microsomal Triglyceride Transfer Protein; PB, Population-Based Controls; PEMT, Phosphatidylethanolamine N-methyltransferase; PNPLA3, Patatin-like Phospholipase Domain Containing 3; PPARγ, Peroxisome Proliferator-Activated Receptor Gamma; SREBF-2, Sterol Regulatory Element-binding Factor 2; TM6SF2, Transmembrane 6 Superfamily Member 2; US, Ultrasonography.