Elevated blood pressure: Our family’s fault? The genetics of essential hypertension

Table 2 Genes with their identified physiological pathway and genes identified with their associated physiological functions related to essential hypertension

Genes	Pathway related to EH
NOS3	RAAS pathway[22]
SH2B3	Endothelial cell function[17]
AGT	Renal electrolyte balance[17]
NPPA	Control of extracellular fluid volume and electrolyte homeostasis[23]
NPPB	Involved in vasorelaxation and inhibition of renin and aldosterone[24]
NPR3	Involved with regulating blood volume and pressure, pulmonary hypertension, and cardiac function[25]
UMOD	Constitutive inhibitor of calcium crystallization in renal fluids[26]
CYP17A1	Involved with steroid/aldosterone synthesis. Enzyme dysfunction leads to increased levels of mineralocorticoid activating hormones[17]
ATP2B1	Codes for enzymes that have a critical role in intracellular calcium homeostasis[27]
CACNB2	Encodes for a subunit of a voltage-dependent calcium channel protein that is a member of the voltage-gated calcium channel superfamily[28]
SLC24A4	Encodes for a member of the potassium-dependent sodium/calcium exchanger protein family[29]
YWHAZ	Protein interacts with insulin receptor substrate 1 protein, suggesting a role in regulating insulin sensitivity[30]
ADAMTS-8	Enzyme encoded by the gene disrupts angiogenesis in vivo[31]
ADM	Protein encoded by gene may function as a hormone in circulation control[32]
c5 site between SUB1 and NPR3	SNP associated with SBP
	NPR3 encodes natriuretic peptide receptor C/guanylate cyclase C for natriuretic peptide clearance[33-35]
	Also found relationship with DBP
CACANA1H	Codes for α1 subunit of voltage-dependent calcium channel for heart contractions and associated with SBP in African Americans[36]
ENPEP	Facilitates production of angiotensinII in RAAS pathway and associated with SBP and DBP[33]
ADD1 and ACE	ADD1 codes for α-adducin protein that interacts with sodium channel of Na/K co-transporter and Na/K ATPase[37]
	Angiotensin converting enzyme produces angiotensin-converting enzyme which converts angiotensin I to angiotensin II in RAAS pathway[38]
ADD2	β-adducin is a cytoskeletal actin-binding protein implicated in glomerular lesions[39]
CYP11B2	Contributes to aldosterone synthesis in RAAS pathway[40]
AGT	Encodes angiotensinogen in RAAS pathway[41]
LOC344371 and RASGRP3	Activation decreases vascular responsiveness to endothelin-1 and angiotensin II in rats[41]
EDN3	Endothelin-3 involved in vasoconstriction[42]
BCAT1	Associated with salt sensitivity[43]
CASZ1	Zinc-finger transcription factor that is associated with DBP[33]
ADRB2	Ion channel involved with regulation of vasoconstriction[12]
CYP11B2	Enzymatic defects results in decreased aldosterone and increased salt-wasting[12,17]
MMP3	Gene variants affect arterial stiffness and endothelial function[44]
NR3C2	Involved with aldosterone signaling[12]
SCNN1B	C terminus deletion leads to reduced ENaC clearance and increased ENaC activity[12]
APLNR	Mediator of cardiovascular disease[45]
BDKRB2	Involved in catecholamine synthesis[46]
MTHFS	Involved with catecholamine binding[47]
SOX6	Required in transcription for maintenance of cardiac and skeletal muscle cells[17]
CACNA1A	Involved with regulating SBP[48]
CCNG1	Involved with regulation of SBP and DBP and is component of regulating hypertension[15]
CPLX3	Involved with regulating DBP[15]
CSK	Cytoplasmic tyrosine kinase involved with angiotensin II-dependent vascular smooth muscle cell contraction[17]
CACNA1C	Regulates calcium influx after depolarization[49]
CLCNKB	Involved in renal salt absorption[50]
EDN1	Endothelin-1 involved in vasoconstriction[51]
EDNRA	Endothelin receptor type A involved in vasoconstriction[52]
KCNJ1	Potassium channel involved with potassium homeostasis[53]
SCNN1A	Involved with renal sodium regulation[54]
SCNN1B	Involved with renal sodium regulation[55]
SCNN1G	Involved with renal sodium regulation[56]
SGK1	Activation of certain potassium, sodium and chloride channels, playing a role in cellular stress response[57]
SLC12A1	Cotransporter involved in sodium and chloride reabsorption in the distal convoluted tubule[58]
SLC12A3	Cotransporter involved in sodium and chloride reabsorption in the loop of Henle[59]
TNNT3	Involved in calcium-induced muscle contraction[60]
WNK1	Kinase involved with sodium and chloride transport[61]
WNK4	Kinase regulates balance between sodium chloride and potassium reabsorption in kidneys[62]
GOSR2	Interacts with target-localized SNAREs, allowing angiotensinogen to move between Golgi compartments, possibly leading to vasoconstriction[63]
GUCY1B3	Receptor for nitric oxide involved with vasodilation[64]
ATXN2	Possible association with regulation of GFR[65]
SLC4A7	Possible transporter of sodium and bicarbonate ions[66]
CDH13	Regulates endothelial cell growth[67]
Identifier information	Gene
Non- European genes	NPR3, IPO7, MYLIP, PMS1, SLC24A4, TBX3, YWHAZ, FIGN-GRB14, ALDH2, c5 site between SUB1 and NPR3, CACANA1H, SNP upstream of CCBE1, ENPEP, ST7L-CAPZA1
Gene-gene interaction	ADD1 and ACE, ADD1 and ADD2, ADD1 and CYP11B2, AGT and ACE, c20q12, IMPG1, LOC344371 and RASGRP3, PCDH15, NPR3-c5orf23, CSK-ULK3, BAT2-BAT5, BLK-GATA4, GNAS-EDN3
Gene- environment interaction	Body Mass Index: ADD1, ADRB2, CAPN13, CYP11B2, CYP19A1, MMP3 Black, Male: AGT Level of physical activity: GNB3, NR3C2, SCNN1B, APLNR, BDKRB2 Oral contraceptive use: COL25A1 Preterm birth: MTHFS
Unknown function/ function could not be determined	GNAS-EDN3, NPR3-c5orf23, BLK-GATA4, ST7L-CAPZA1, CSK-ULK3, FIGN-GRB14, c10orf107, c21orf91, LSP1-TNNT3, GNAS-EDN3, BAT2, IPO7, MYLIP, PMS1, TBX3, TBX4, TBX5, ANKMY, BAT2, BAT3, BAT4, BAT5, ALDH2, SNP upstream of CCBE1, BCAT1, PCDH15, c20q12, IMPG1, CAPN13, CYP19A1, GNB3, COL25A1, PCDH15, IMPG1, c5 site between SUB1 and NPR3, CHIC2-PDGRA1, APOB, HFE, CYPBA, CYP1A2, CYP2C8, EBF1, FES, FGF5, FIGN, FLJ32810, GNB3, LSP1, NOS3, TMEM133, FOXD3, GPR98, ARRDC3, GUCY1A3, JAG1, MECOM (MD1 locus), MOV10, NOV, NPR3-c5orf23, NT5C2-CYP171A, PIK3CG, PLCD3, PLCE1, PLEKHA7, RPL6-PTPN11-ALDH2, SLC39A8, ULK4, ZNF652, CCL20, WDR69, TGFBR2, STK39

Only genes with pathways related to EH were identified. Genes identified with their associated physiological functions associated with EH. If there were genes that coded for proteins, but these proteins were not found to affect EH, then it was listed as unknown function or the function could not be determined. Genes with hyphens indicate genome wide association studies associated genomic regionsin, in which the genetic pathway could not be determined and properly evaluated for its involvement with EH. EH: Essential hypertension; RAAS: Renin-angiotensin-aldosterone system; SBP: Stolic blood pressure; DBP: Diastolic blood pressure.