Table 3.
Retrospective Candidate Gene Studies Linking Genetic Variants to NAFLD.
| Gene | SNP | Study population | Notable cohort characteristics | Sample size | Diagnostic modality |
|---|---|---|---|---|---|
| ABCC2 | rs17222723, rs818771062 | Argentine | Poor selection of controls | 109 cases/58 controls | US |
| ACSL4 | rs788798163 | Finnish | Validated in 2 replication cohorts | 302 total with replication cohorts | 1H-MRS |
| ADIPOR2 | rs76787063 | Finnish | Validated in 2 replication cohorts | 302 total with replication cohorts | 1H-MRS |
| ADRB2 | rs104271464 | Japanese | – | 132 cases/119 controls | US |
| ADRB3 | rs499465 | Japanese | Exclusively NASH cases | 63 cases/100 controls | CT |
| AGTR1 | rs3772630, rs377262266 | Japanese | 80% males in NAFLD cases | 167 cases/435 controls | Liver biopsy |
| APOE | rs7412, rs42935867 | Turkish | – | 57 cases/245 controls | Liver biopsy |
| APPL1 | rs464052568 | Chinese | – | 280 cases/281 controls | Unreported |
| FADS1 | rs17455669 | American and Chinese | Analysis of explanted liver samples | 206 transplants | Histology of donor livers |
| GCLC/GCLM | rs1788390170 | Brazilian | – | 131 cases/141 controls | Liver biopsy |
| IL-1 | rs1694465 | Japanese | Exclusively NASH cases | 63 cases/100 controls | CT |
| IL-6 | rs180079571 | Italian | Poor selection of controls | 114 cases/79 controls | Liver biopsy in 59/114 cases |
| LEPR | rs670098672 | Egyptian | – | 90 cases/30 controls | Liver biopsy |
| rs1137100, rs113710173 | Malaysian, Chinese, Indian | – | 144 cases/198 controls | Liver biopsy | |
| LYPLAL1 | rs1213785584 | Chinese | – | 184 cases/114 controls | US |
| MBOAT7 | rs64173874 | American and European | – | 3854 total in Dallas Heart Study, 1149 total in Liver Biopsy Cohort | Liver biopsy and 1H-MRS |
| NCAN | rs222860375 | American | Bariatric cohort; 80% female subjects; Ethnicities not reported | 748 cases/344 controls | Liver biopsy |
| PARVB | rs5764455, rs600647376 | Chinese | 60% male subjects | 384 cases/384 controls | US |
| PPP1R3B | rs424062477 | American | Population-based | 4804 total | US |
| SAMM50 | rs738491, rs2143571, rs376147285 | Chinese | – | 340 cases/452 controls | US |
| SLC2A1 | rs4658, rs84185678 | Spanish | Poor selection of controls | 451 cases/304 controls | Liver biopsy |
| SOD2 | rs488079 | Chinese | – | 131 cases/90 controls | Liver biopsy |
| TCF7L2 | rs790314680 | Italian | ∼75% male subjects | 78 cases/156 controls | Liver biopsy in 34/78 cases |
| TLR4 | rs498679081 | Turkish | – | 119 cases/80 controls | Liver biopsy in 111/119 cases |
| TRAIL | rs1131568, rs113158082 | Chinese | – | 84 cases/80 controls | Unreported |
| UCP3 | rs1123597283 | Spanish | – | 39 cases | Liver biopsy |
| 11β-HSD1 | rs2235543, rs12565406, rs4844880111 | German | 100% Caucasian All subjects had family history of T2DM, BMI > 27, or impaired glucose tolerance testing |
327 total subjects | 1H-MRS |
| CD14 | C159T polymorphism112 | Indian | 64% male subjects | 200 NAFLD/50 controls | US |
| Omentin-1 | rs2274907113 | Iranian | Significantly lower BMI in control group | 94 NAFLD/188 controls | US |
| PTPRD | rs35929428114 | Japanese | Significantly lower age in control group | 36 NAFLD/27 controls | Liver biopsy |
| Resistin | rs1862513113 | Iranian | Significantly lower BMI in control group | 94 NAFLD/188 controls | US |
a These studies have demonstrated no association with NAFLD.
ABCC2, ATP-binding Cassette, Sub-family C, Member 2; ACSL4, Acyl-coA Synthase Long Chain Family Member 4; ADIPOR2, Adiponectin Receptor 2; ADRB2, Adrenergic Beta 2 Receptor; ADRB3, Adrenergic Beta 3 Receptor; AGTR1, Angiotensin II Type 1 Receptor; APOE, Apolipoprotein E; APPL1, Adaptor Protein, Phosphotyrosine Interacting with PH Domain and Leucine Zipper 1; CT, Computed Tomography; FADS1, Fatty Acid Desaturase 1; GCLC/GCLM, Glutamate-cysteine Ligase; 1H-MRS, Proton Magnetic Resonance Spectroscopy; IL-1, Interleukin-1; IL-6, Interleukin-6; LEPR, Leptin Receptor; LYPLAL1, Lysophospholipase-like 1; MBOAT7, Membrane Bound O-acyltransferase Domain-containing 7 Gene; NCAN, Neurocan; PARVB, Parvin Beta; PPP1R3B, Protein Phosphatase 1 Regulatory Subunit 3B; SAMM50, Sorting and Assembly Machinery Component 50; SLC2A1, Solute Carrier Family 2 Member 1; SOD2, Superoxide Dismutase 2, Mitochondrial; TCF7L2, Transcription Factor 7-like 2; TLR4, Toll-like Receptor 4; TRAIL, TNF-related Apoptosis-inducing Ligand; UCP3, Uncoupling Protein 3, Mitochondrial; 11β-HSD1, 11β-Hydroxysteroid Dehydrogenase Type 1; CD14, Coreceptor Cluster of Differentiation 14; PTPRD, Receptor-type Tyrosine-protein Phosphatase Delta; US, Ultrasonography.