Table 1. SNVs associated with renin-angiotensin-aldosterone system and metabolic pathways involved in ACE inhibitor metabolism.
| SNV | p-value | Gene | Function |
|---|---|---|---|
| rs10864772 | 0.01 | AGT | The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The protein is involved in maintaining blood pressure and in the pathogenesis of essential hypertension. Mutations in this gene are associated with susceptibility to essential hypertension |
| rs11240695 | 0.02 | REN | Renin catalyzes the first step in the activation pathway of angiotensinogen which leads to aldosterone release, vasoconstriction, and increase in blood pressure. Renin cleaves angiotensinogen to form angiotensin I, which is converted to angiotensin II by ACE, an important regulator of blood pressure. |
| rs4240157 | < 0.01 | ACE2 | Angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases. Catalyzes the cleavage of angiotensin I into angiotensin, and angiotensin II into the vasodilator angiotensin. |
| rs73107462 | < 0.01 | KCNIP4 | KCNIP4 regulates Kv4 potassium channels. Mutation in KCNIP4 gene may lead to stimulation of sensory nerve afferents within the lung from accumulation of bradykinin. |
| rs17520919 | < 0.01 | ||
| rs358826 | 0 < 0.01 | ||
| rs1398831 | < 0.01 | ||
| rs6838195 | < 0.01 | ||
| rs10000092 | 0.01 | ||
| rs56807277 | 0.02 | ||
| rs16869949 | 0.01 | ||
| rs1352798 | 0.02 | ||
| rs60028998 | 0.02 | ||
| rs16870400 | 0.03 | ||
| rs7683672 | 0.03 | ||
| rs9991631 | 0.03 | ||
| rs2137650 | 0.03 | ||
| rs6850480 | 0.03 | ||
| rs73801665 | 0.03 | ||
| rs16870831 | 0.03 | ||
| rs1495522 | 0.04 | ||
| rs11734403 | 0.05 | ||
| rs114695525 | 0.05 | ||
| rs7649252 | 0.01 | MME |
MME encodes neprilysin which breaks down bradykinin along with ACE. Neprilysin along with ACE degrades vasoactive peptides such as bradykinin and substance P. |
| rs9853221 | 0.02 | ||
| rs4149063 | 0.04 | SLCO1B1 | SLCO1B1 encodes an organic anion transporter protein, OATP1B1, which is involved in hepatic drug clearance of enalapril. Both ACEIs and ARBs [8] are partly transported into bile and cleared from the plasma by the OATP1B1 transporter. |
SNV = single nucleotide variant; ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker.