Abstract
IntroductionSeveral common and functional genes are known to contribute to renal, blood vessel, and cardiac functional characteristics associated with sodium (Na+) handling, vascular reactivity, and cardiac output, respectively. Many of these same genes are suggested to contribute to differential responsiveness to blood pressure (BP) therapy. Few studies have explored the simultaneous phenotypic consequence of multiple genes critical for BP control. Despite a significant impulse of the medical community towards personalized medicine, BP therapy is typically guided by algorithms that do not include a patient's genetic information.PurposeThe purpose of this study was to determine the impact of 14 genes on time to BP control in response to common BP therapy, with a specific focus on genes associated with drug metabolism and protein function in the kidney, the blood vessels, and the heart.MethodsEighty‐six patients completed one study visit consisting of a buccal swab for DNA extraction and genotyping, measurement of ambulatory BP, and a medical chart review for objective BP history. Genes in the analysis included those that encode for one drug metabolizing enzyme (CYP2D6), renal Na+ handling (SCNN1A, WNK1, SLC12A3, and Alpha Adducin), vascular function (angiotensin, ACE, angiotensin‐II receptor type‐I, and renin), and cardiac function (the β1 and β2 adrenergic receptors ADRB1 and ADRB2, respectively).ResultsGenetic variation of WNK1 (rs1159744) demonstrated differential responses to diuretic therapy (determined as those with blood pressure under 140/90 vs. those above 140/90 according to genotype)(WNK1=GG>CG/CC, P<0.05). Genes that encode ADRB1 (rs1801252), ADRB2 (rs1042713), and CYP2D6 (rs3892097) demonstrated differential response to β‐blocker therapy (ADRB1=Ser/Ser>SerThr/ThrThr, ADRB2=GG>AG/AA, CYP2D6=CC>CT/TT, P<0.05). Genes that encode angiotensin (rs699), ACE (rs1799752), and renin (rs12750834) demonstrated differential response to ACE‐inhibition and angiotensin receptor blockade (angiotensin=CT/TT>CC, ACE=Ins/Ins>InsDel/DelDel, renin=AG/AA>GG, p<0.05).ConclusionThese results demonstrate that genetic variants encoding proteins involved in renal Na+ handling, vascular function, and cardiac output influence response to BP therapy for their respective drug classes.Support or Funding InformationFunded by Geneticure
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