Table 1.
Gene (Name)*/Reference(s) | Mechanism(s) | Human Evidence | Animal Evidence |
---|---|---|---|
CYP17A1 (cytochrome P-450 enzyme) (66, 78 | Pathways of steroid synthesis | Congenital adrenal hyperplasia (MIM no. 202110) | |
ADM (adrenomedullin) (28, 97) | Vasodilation and angiogenesis promotion | Protein found in human pheochromocytoma | |
NPPA/NPPB (natriuretic peptide A and B) (77) | Precursors for atrial- and B-type natriuretic peptides | ||
NPR3 (natriuretic peptide clearance receptor) (28, 59, 97) | Natriuretic pathways | ||
GUCY1A3-GUCY1B3 (α− and β−subunits of soluble guanylate cyclase) (28, 97) | Both units form the guanylate cyclase enzyme that activates nitric oxide. Vasodilatory mechanism for nitrovasodilator drugs | Knockout mice of either gene develop hypertension (36). | |
EDN3 (endothelin 3) (65, 97) | Potent vasoconstrictor | ||
SLC4A7 (electroneutral sodium bicarbonate cotransporter) (28, 97) | Kidney sodium-bicarbonate cotransporter | ||
PLCE1 (phospholipase C-epsilon-1 isoform) (28) | Podocyte development | Nephrotic syndrome type 3 (MIM no. 610725) | |
HFE (hemochromatosis) (28, 97) | Ion transport (iron); diabetes | Hemochromatosis (MIM no. 613609) | |
SLC39A8 (solute carrier family 39, zinc transporter) (28, 97) | Ion transport (cadmium) | ||
ENPEP (glutamyl aminopeptidase (aminopeptidase A) (59) | Glutamyl aminopeptidase facilitates conversion of angiotensinogen II | ||
ATP2B1 (ATPase, Ca2+ transporting, plasma membrane 1) (16, 59, 65, 96) | Calcium homeostasis | VSMC target tissue knockout mice show higher blood pressure than wild-type and augmented vasoconstrictive response of femoral artery to phenylephrine stimulation (62). | |
NOS3 (nitric oxide synthase 3 (endothelial cell) (91) | Vasodilatory effects | ||
PIK3CG (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma) (97) | Mice lacking PIK3γ have shown resistance to the SBP-lowering effects of β-adrenergic receptor agonist (82). | ||
NOV (nephroblastoma overexpressed) (28, 94) | Angiogenesis, proliferation and inhibition of vascular smooth muscle cell growth and migration (29) | Mice null for the nephroblastoma-overexpressed protein (CCN3) have reduced neointimal thickening (93). | |
ADRB1 (adrenoceptor beta 1) (97) | Mediates physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine | Associated with resting heart rate in humans (88) |
VSMC, vascular smooth muscle cells; SBP, systolic blood pressure.
Listed genes are from genome-wide association scans (GWAS) studies.