Table 1.

CAD Genes Associated With CAD and Lipid Phenotypes in GWASs That Are Used as Therapeutic Targets

Gene	Protein/Mechanism	Clinical Use/Perspective	Ref. #
APOC3	Apolipoprotein C-3/lipoprotein lipase activity ⇓, plasma triglycerides ⇑ → increased CAD risk	Antisense APOC3 inhibitor (Volanesorsen) leads to a dose-dependent 31%–71% reduction in triglycerides, effective triglyceride reduction in familial chylomicronemia syndrome	(60, 61, 62, 63)
ANGPTL3/4	Angiopoietin-like protein 3/4/Lipoprotein lipase activity ⇓, plasma triglycerides ⇑ → increased CAD risk	Evinacumab, a monoclonal antibody against ANGPTL3, reduced plasma LDL-cholesterol levels in patients with familial hypercholesterolemia by 47%	(60,64, 65, 66, 67, 68, 69, 70)
PCSK9	Proprotein convertase subtilisin/kexin type 9/LDL-cholesterol receptor recycling on the hepatocellular surface ⇓, LDL-cholesterol receptor density ⇓, LDL-cholesterol ⇑ → increased CAD risk	Monoclonal antibodies and antisense molecules reduce PCSK9 function and LDL-cholesterol and cardiovascular events	(9,50,71, 72, 73, 74, 75)
LPA	Lipoprotein(a)/lipoprotein with prothrombotic and proinflammatory properties → increased CAD risk	Lipoprotein(a) can be reduced by lipid apheresis; TQJ230, an antisense oligomer, is currently investigated in clinical trials (NCT04023552∗)	(76, 77, 78, 79, 80)
NPC1L1	Niemann-Pick C1-Like 1/Involved in the resorption of cholesterol from the intestine, LDL-cholesterol ⇑ → increased CAD risk	Ezetimibe, a NPC1L1 inhibitor, was able to reduce LDL-cholesterol and cardiovascular events when added to statin therapy	(78,81,82)
HMGCR	3-Hydroxy-3-methylglutaryl-CoA reductase/pivotal in endogenous cholesterol biosynthesis, LDL-cholesterol ⇑ → increased CAD risk	Statins targeting 3-hydroxy-3-methylglutaryl-CoA reductase have been repeatedly shown to reduce cardiovascular events	(83,84)

CAD = coronary artery disease; CoA = coenzyme A; GWASs = genome-wide association studies; LDL = low-density lipoprotein; PCSK9 = proprotein convertase subtilisin/kexin type 9.

^∗Assessing the Impact of Lipoprotein (a) Lowering With TQJ230 on Major Cardiovascular Events in Patients With CVD [Lp(a)HORIZON].