Gene variants with large effect sizes (-3.5 to +3.5 mm Hg difference per allele) explained a large proportion of the difference in antihypertensive response between black and white individuals.
Meta-Analysis (n=4,696)
Yes
Do genetically defined ancestry and specific gene variants better explain variation in blood pressure response to antihypertensive drugs compared to self-defined ethnicity?
Genetically defined ancestry and specific gene variants explain differences in antihypertensive drug response better than self-defined ethnicity, supporting a genomic precision medicine approach over race-based prescribing.
Effect estimate: -3.5 to +3.5 mm Hg per allele
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.
Iniesta et al. (Mon,) conducted a meta-analysis in Hypertension (n=4,696). Genetically defined ancestry and gene variants vs. Self-defined ethnicity was evaluated on Blood pressure response to antihypertensive drugs (-3.5 to +3.5 mm Hg per allele). Gene variants with large effect sizes (-3.5 to +3.5 mm Hg difference per allele) explained a large proportion of the difference in antihypertensive response between black and white individuals.