Gene variants at loci related to blood pressure account for variation in response to antihypertensive drugs between black and white individuals: Genomic precision medicine may dispense with ethnicity

Raquel Iniesta, Desmond Campbell, Cristina Venturini, Luca Faconti, Sonal Singh, Marguerite R. Irvin, Rhonda M. Cooper-Dehoff, Julie A. Johnson, Stephen T. Turner, Donna K. Arnett, Michael E. Weale, Helen Warren, Patricia B. Munroe, Kennedy Cruickshank, Sandosh Padmanabhan, Cathryn Lewis, Phil Chowienczyk

Research output: Contribution to journalArticle

Abstract

Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compared the extent to which variation in blood pressure response across different ethnicities may be explained by genetic factors: genetically defined ancestry and gene variants at loci known to be associated with blood pressure. We analyzed data from 5 trials in which genotyping had been performed (n=4696) and in which treatment responses to β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, thiazide or thiazide-like diuretic and calcium channel blocker were available. Genetically defined ancestry for proportion of African ancestry was computed using the 1000 genomes population database as a reference. Differences in response to the thiazide diuretic hydrochlorothiazide, the β-blockers atenolol and metoprolol, the angiotensin-converting enzyme inhibitor lisinopril, and the angiotensin receptor blocker candesartan were more closely associated to genetically defined ancestry than self-defined ethnicity in admixed subjects. A relatively small number of gene variants related to loci associated with drug-signaling pathways (KCNK3, SULT1C3, AMH, PDE3A, PLCE1, PRKAG2) with large effect size (-3.5 to +3.5 mm Hg difference in response per allele) and differing allele frequencies in black versus white individuals explained a large proportion of the difference in response to candesartan and hydrochlorothiazide between these groups. These findings suggest that a genomic precision medicine approach can be used to individualize antihypertensive treatment within and across populations without recourse to surrogates of genetic structure such as self-defined ethnicity.

Original languageEnglish (US)
Pages (from-to)614-622
Number of pages9
JournalHypertension
Volume74
Issue number3
DOIs
StatePublished - Sep 1 2019

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Precision Medicine
Antihypertensive Agents
Sodium Chloride Symporter Inhibitors
Hydrochlorothiazide
Angiotensin Receptor Antagonists
Blood Pressure
Angiotensin-Converting Enzyme Inhibitors
Genes
Lisinopril
Thiazides
Metoprolol
Atenolol
Genetic Structures
Calcium Channel Blockers
Gene Frequency
Population
Therapeutics
Alleles
Genotype
Genome

Keywords

  • antihypertensive agents
  • blood pressure
  • ethnic
  • genotype
  • groups
  • pharmacogenetics

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Gene variants at loci related to blood pressure account for variation in response to antihypertensive drugs between black and white individuals : Genomic precision medicine may dispense with ethnicity. / Iniesta, Raquel; Campbell, Desmond; Venturini, Cristina; Faconti, Luca; Singh, Sonal; Irvin, Marguerite R.; Cooper-Dehoff, Rhonda M.; Johnson, Julie A.; Turner, Stephen T.; Arnett, Donna K.; Weale, Michael E.; Warren, Helen; Munroe, Patricia B.; Cruickshank, Kennedy; Padmanabhan, Sandosh; Lewis, Cathryn; Chowienczyk, Phil.

In: Hypertension, Vol. 74, No. 3, 01.09.2019, p. 614-622.

Research output: Contribution to journalArticle

Iniesta, R, Campbell, D, Venturini, C, Faconti, L, Singh, S, Irvin, MR, Cooper-Dehoff, RM, Johnson, JA, Turner, ST, Arnett, DK, Weale, ME, Warren, H, Munroe, PB, Cruickshank, K, Padmanabhan, S, Lewis, C & Chowienczyk, P 2019, 'Gene variants at loci related to blood pressure account for variation in response to antihypertensive drugs between black and white individuals: Genomic precision medicine may dispense with ethnicity', Hypertension, vol. 74, no. 3, pp. 614-622. https://doi.org/10.1161/HYPERTENSIONAHA.118.12177
Iniesta, Raquel ; Campbell, Desmond ; Venturini, Cristina ; Faconti, Luca ; Singh, Sonal ; Irvin, Marguerite R. ; Cooper-Dehoff, Rhonda M. ; Johnson, Julie A. ; Turner, Stephen T. ; Arnett, Donna K. ; Weale, Michael E. ; Warren, Helen ; Munroe, Patricia B. ; Cruickshank, Kennedy ; Padmanabhan, Sandosh ; Lewis, Cathryn ; Chowienczyk, Phil. / Gene variants at loci related to blood pressure account for variation in response to antihypertensive drugs between black and white individuals : Genomic precision medicine may dispense with ethnicity. In: Hypertension. 2019 ; Vol. 74, No. 3. pp. 614-622.
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