Iniesta, R;
Campbell, D;
Venturini, C;
Faconti, L;
Singh, S;
Irvin, MR;
Cooper-DeHoff, RM;
... Chowienczyk, P; + view all
(2019)
Gene Variants at Loci Related to Blood Pressure Account for Variation in Response to Antihypertensive Drugs Between Black and White Individuals.
Hypertension
, 74
(3)
pp. 614-622.
10.1161/HYPERTENSIONAHA.118.12177.
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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.
| Type: | Article |
|---|---|
| Title: | Gene Variants at Loci Related to Blood Pressure Account for Variation in Response to Antihypertensive Drugs Between Black and White Individuals |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1161/HYPERTENSIONAHA.118.12177 |
| Publisher version: | https://doi.org/10.1161/HYPERTENSIONAHA.118.12177 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | ancestry, antihypertensive drugs, blood pressure, ethnicity, race |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10095739 |
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