Table 1 Summary of genetically proxied lipid-lowering drug targets
Drug Effect | Drug Class | Drug Target | Encoding Genes | Gene Location (GRCh37 from Ensembl) | Drug Substance | Eligible IVs |
|---|---|---|---|---|---|---|
↓LDL-C | Key Modulater | LDL Receptor | LDLR | CHR:19:11,200,038-11,244,492 | – | yes |
HMGCR inhibitors | HMG-CoA reductase | HMGCR | CHR:5:74,632,154-74,657,929 | Atorvastatin Rosuvastatin etc. | yes | |
ACLY inhibitors | ATP-citrate synthase | ACLY | CHR:17:40,023,161-40,086,795 | Bempedoic acid | no | |
PCSK9 inhibitors | Proprotein Convertase Subtilisin/Kexin Type 9 | PCSK9 | CHR:1:55,505,221-55,530,525 | Evolocumab Alirocumab | yes | |
TC absorption inhibitors | Niemann-Pick C1-like 1 | NPC1L1 | CHR:7:44,552,134-44,580,914 | Ezetimibe | yes | |
ASO targeting ApoB mRNA | Apo B100 | APOB | CHR:2:21,224,301-21,266,945 | Mipomersen | yes | |
ASO targeting CETP mRNA | Cholesteryl Ester Transfer Protein | CETP | CHR:16:56,995,762-57,017,757 | Torcetrapib | yes | |
BA sequestrants | Bile acids | – | – | Cholestyramine Colestipol | no | |
↓TG | Key Modulater | Lipoprotein Lipase | LPL | CHR:8:19,759,228-19,824,769 | – | yes |
Fibrates | Peroxisome Proliferator-Activated Receptor-alpha | PPARA | CHR:22:46,546,424-46,639,653 | Fenofibrate Gemfibrozil | no | |
ANGPTL3 inhibitors | Angiopoietin-related protein 3 | ANGPTL3 | CHR:1:63,063,158-63,071,830 | Evinacumab | yes | |
ASO targeting ApoC-III mRNA | Apo C-III | APOC3 | CHR:11:116,700,422-116,703,788 | Volanesorsen | yes |