Copyright
©The Author(s) 2019.
World J Gastroenterol. Apr 21, 2019; 25(15): 1783-1796
Published online Apr 21, 2019. doi: 10.3748/wjg.v25.i15.1783
Published online Apr 21, 2019. doi: 10.3748/wjg.v25.i15.1783
Table 1 Non-alcoholic fatty liver disease-Kyoto Encyclopedia of Genes and Genomes pathway (hsa04932)
| Gene symbol; description |
| IL6; interleukin 6 |
| IL6R; interleukin 6 receptor |
| SOCS3; suppressor of cytokine signaling 3 |
| TNF; tumor necrosis factor |
| TNFRSF1A; TNF receptor superfamily member 1A |
| NFKB1; nuclear factor kappa B subunit 1 |
| RELA; RELA proto-oncogene, NF-kB subunit |
| INS; insulin |
| INSR; insulin receptor |
| IRS1; insulin receptor substrate 1 |
| IRS2; insulin receptor substrate 2 |
| PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha |
| PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta |
| PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta |
| PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 |
| PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 |
| PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 |
| AKT1; AKT serine/threonine kinase 1 |
| AKT2; AKT serine/threonine kinase 2 |
| AKT3; AKT serine/threonine kinase 3 |
| GSK3A; glycogen synthase kinase 3 alpha |
| GSK3B; glycogen synthase kinase 3 beta |
| NR1H3; nuclear receptor subfamily 1 group H member 3 |
| RXRA; retinoid X receptor alpha |
| SREBF1; sterol regulatory element binding transcription factor 1 |
| MLX; MLX, MAX dimerization protein |
| MLXIP; MLX interacting protein |
| MLXIPL; MLX interacting protein like |
| PKLR; pyruvate kinase L/R |
| LEP; leptin |
| LEPR; leptin receptor |
| ADIPOQ; adiponectin, C1Q and collagen domain containing |
| ADIPOR1; adiponectin receptor 1 |
| ADIPOR2; adiponectin receptor 2 |
| PRKAA1; protein kinase AMP-activated catalytic subunit alpha 1 |
| PRKAA2; protein kinase AMP-activated catalytic subunit alpha 2 |
| PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 |
| PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 |
| PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 |
| PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 |
| PRKAG2; protein kinase AMP-activated non-catalytic subunit gamma 2 |
| PPARA; peroxisome proliferator activated receptor alpha |
| CDC42; cell division cycle 42 |
| RAC1; Rac family small GTPase 1 |
| MAP3K11; mitogen-activated protein kinase kinase kinase 11 |
| MAPK8; mitogen-activated protein kinase 8 |
| MAPK10; mitogen-activated protein kinase 10 |
| MAPK9; mitogen-activated protein kinase 9 |
| ITCH; itchy E3 ubiquitin protein ligase |
| ERN1; endoplasmic reticulum to nucleus signaling 1 |
| TRAF2; TNF receptor associated factor 2 |
| MAP3K5; mitogen-activated protein kinase kinase kinase 5 |
| JUN; Jun proto-oncogene, AP-1 transcription factor subunit |
| IL1A; interleukin 1 alpha |
| IL1B; interleukin 1 beta |
| IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta |
| XBP1; X-box binding protein 1 |
| CEBPA; CCAAT enhancer binding protein alpha |
| CYP2E1; cytochrome P450 family 2 subfamily E member 1 |
| FASLG; Fas ligand |
| CXCL8; C-X-C motif chemokine ligand 8 |
| TGFB1; transforming growth factor beta 1 |
| EIF2AK3; eukaryotic translation initiation factor 2 alpha kinase 3 |
| EIF2S1; eukaryotic translation initiation factor 2 subunit alpha |
| ATF4; activating transcription factor 4 |
| DDIT3; DNA damage inducible transcript 3 |
| BCL2L11; BCL2 like 11 |
| BAX; BCL2 associated X, apoptosis regulator |
| FAS; Fas cell surface death receptor |
| CASP8; caspase 8 |
| BID; BH3 interacting domain death agonist |
| CYCS; cytochrome c, somatic |
| CASP3; caspase 3 |
| CASP7; caspase 7 |
| NDUFV1-3; NADH:ubiquinone oxidoreductase core subunit V1 –V3 |
| NDUFA1-3; NADH:ubiquinone oxidoreductase subunit A1-3 |
| NDUFA4; NDUFA4, mitochondrial complex associated |
| NDUFA4L2; NDUFA4, mitochondrial complex associated like 2 |
| NDUFA5-13; NADH:ubiquinone oxidoreductase subunit A5-A13 |
| NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 |
| NDUFB1-11; NADH:ubiquinone oxidoreductase subunit B1-B11 |
| NDUFS1-S8; NADH:ubiquinone oxidoreductase core subunit S1 –S8 |
| NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 |
| NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 |
| NDUFC2-KCTD14; NDUFC2-KCTD14 readthrough |
| SDHA; succinate dehydrogenase complex flavoprotein subunit A |
| SDHB; succinate dehydrogenase complex iron sulfur subunit B |
| SDHC; succinate dehydrogenase complex subunit C |
| SDHD; succinate dehydrogenase complex subunit D |
| UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 |
| CYTB; cytochrome b |
| CYC1; cytochrome c1 |
| UQCRC1; ubiquinol-cytochrome c reductase core protein 1 |
| UQCRC2; ubiquinol-cytochrome c reductase core protein 2 |
| UQCRH; ubiquinol-cytochrome c reductase hinge protein |
| UQCRHL; ubiquinol-cytochrome c reductase hinge protein like |
| UQCRB; ubiquinol-cytochrome c reductase binding protein |
| UQCRQ; ubiquinol-cytochrome c reductase complex III subunit VII |
| UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X |
| UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI |
| COX3; cytochrome c oxidase III |
| COX1; cytochrome c oxidase subunit I |
| COX2; cytochrome c oxidase subunit II |
| COX4I2; cytochrome c oxidase subunit 4I2 |
| COX4I1; cytochrome c oxidase subunit 4I1 |
| COX5A; cytochrome c oxidase subunit 5A |
| COX5B; cytochrome c oxidase subunit 5B |
| COX6A1; cytochrome c oxidase subunit 6A1 |
| COX6A2; cytochrome c oxidase subunit 6A2 |
| COX6B1; cytochrome c oxidase subunit 6B1 |
| COX6B2; cytochrome c oxidase subunit 6B2 |
| COX6C; cytochrome c oxidase subunit 6C |
| COX7A1; cytochrome c oxidase subunit 7A1 |
| COX7A2; cytochrome c oxidase subunit 7A2 |
| COX7A2L; cytochrome c oxidase subunit 7A2 like |
| COX7B; cytochrome c oxidase subunit 7B |
| COX7B2; cytochrome c oxidase subunit 7B2 |
| COX7C; cytochrome c oxidase subunit 7C |
| COX8C; cytochrome c oxidase subunit 8C |
| COX8A; cytochrome c oxidase subunit 8A |
Table 2 Associations between variants in locus that are targets of novel drugs for the treatment of nonalcoholic steatohepatitis and multiple traits from individuals of the United Kindom Biobank
| Trait | Variant | Position | -log10(p-value) |
| NR1H4 (FXR) Farnesoid X-Activated Receptor | |||
| K85 Acute pancreatitis | rs76372051 | 100945711 | 6.963890333 |
| Immature reticulocyte fraction | rs35712 | 100971355 | 5.607954097 |
| Impedance of arm (right) | rs1409791 | 100851307 | 5.152661824 |
| Impedance of whole body | rs1409791 | 100851307 | 4.772216099 |
| migraine | rs12579460 | 100966714 | 4.639293011 |
| high cholesterol | rs7967468 | 100853792 | 4.543497322 |
| N30-N39 Other diseases of urinary system | rs79306023 | 100938470 | 4.420628035 |
| H81 Disorders of vestibular function | rs140644635 | 100923359 | 4.069764347 |
| PPARδ (Peroxisome Proliferator Activated Receptor Delta) | |||
| Whole body fat-free mass | rs36018387 | 35386872 | 59.74853212 |
| Hip circumference | rs36018387 | 35386872 | 49.20670564 |
| Whole body fat mass | rs36018387 | 35386872 | 37.00113934 |
| Body fat percentage | rs36018387 | 35386872 | 20.45328464 |
| Monocyte percentage | rs9469982 | 35267548 | 45.86340625 |
| Platelet crit | rs33959228 | 35259397 | 21.6726615 |
| White blood cell (leukocyte) count | rs9380500 | 35266231 | 21.54556677 |
| Platelet count | rs9658111 | 35364534 | 17.88276186 |
| Neutrophill count | rs9380500 | 35266231 | 17.11253462 |
| Eosinophill percentage | rs2395625 | 35405461 | 15.34904201 |
| Lymphocyte percentage | rs9658079 | 35327577 | 9.741626151 |
| asthma | rs1557568 | 35260530 | 9.184130164 |
| K90 Intestinal malabsorption | rs7771474 | 35320447 | 11.86097145 |
| MPC1 (Mitochondrial Pyruvate Carrier 1) | |||
| Mean platelet (thrombocyte) volume | rs10946160 | 166757818 | 7.378512135 |
| Platelet count | rs3728 | 166778679 | 5.285527735 |
| Red blood cell (erythrocyte) count | rs6916128 | 166759313 | 4.825911105 |
| M31 Other necrotising vasculopathies | rs7449594 | 166774429 | 4.699926505 |
| dyspepsia / indigestion | rs6909951 | 166758198 | 4.594790286 |
| MAP3K5 (ASK-1) (Mitogen-Activated Protein Kinase Kinase Kinase 5) | |||
| Mean platelet (thrombocyte) volume | rs6924387 | 137082948 | 14.48853109 |
| Eosinophill count | rs932589 | 137083138 | 13.39556873 |
| Lymphocyte percentage | rs6924387 | 137082948 | 10.84396601 |
| Neutrophill count | rs6924387 | 137082948 | 10.59715422 |
| Platelet count | rs9321570 | 137095679 | 9.792150289 |
| White blood cell (leukocyte) count | rs6924387 | 137082948 | 9.574319083 |
| Eosinophill percentage | rs932589 | 137083138 | 9.344890391 |
| Monocyte count | rs9385775 | 137144920 | 9.1157769 |
| Mean reticulocyte volume | rs9385775 | 137144920 | 8.817927896 |
| Platelet distribution width | rs6924387 | 137082948 | 8.001963098 |
| THRβ (Thyroid Hormone Receptor Beta) | |||
| Mean corpuscular volume | rs869785 | 24347800 | 152.2743497 |
| Mean corpuscular haemoglobin | rs869784 | 24348008 | 143.9371173 |
| Red blood cell (erythrocyte) count | rs869785 | 24347800 | 61.9076303 |
| Mean reticulocyte volume | rs869784 | 24348008 | 43.97976306 |
| Reticulocyte count | rs1505307 | 24343330 | 16.57632823 |
| Immature reticulocyte fraction | rs869784 | 24348008 | 15.67096843 |
| Monocyte count | rs12485694 | 24346109 | 11.11788547 |
| Lymphocyte count | rs13096529 | 24232035 | 10.58643203 |
| Red blood cell (erythrocyte) distribution width | rs2167115 | 24339734 | 10.44361306 |
| C56 Malignant neoplasm of ovary | rs189397255 | 24389732 | 12.2277003 |
| Trunk fat-free mass | rs13100197 | 24491484 | 8.731024419 |
| Trunk predicted mass | rs13100197 | 24491484 | 8.614769205 |
| Leg fat percentage (left) | rs1349265 | 24159387 | 8.323233252 |
- Citation: Sookoian S, Pirola CJ. Repurposing drugs to target nonalcoholic steatohepatitis. World J Gastroenterol 2019; 25(15): 1783-1796
- URL: https://www.wjgnet.com/1007-9327/full/v25/i15/1783.htm
- DOI: https://dx.doi.org/10.3748/wjg.v25.i15.1783