4.7 Article

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

期刊

HYPERTENSION
卷 74, 期 3, 页码 614-622

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.118.12177

关键词

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

资金

  1. Medical Research Council
  2. British Heart Foundation
  3. Department of Health via a National Institute for Health Research (NIHR) Biomedical Research Centre and Clinical Research Facility award
  4. King's College London
  5. NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London
  6. National Institute of Health Pharmacogenetics Research Network [U01-GM074492]
  7. National Center for Advancing Translational Sciences [UL1 TR000064, UL1 TR000135, UL1 TR000454]
  8. National Institutes of Health (NIH) Heart, Lung, and Blood Institute [5 R01 HL-63082]
  9. National Heart, Lung, and Blood Institute
  10. NIH Heart, Lung, and Blood Institute [1R01HL103612]
  11. MRC [MR/M016560/1] Funding Source: UKRI

向作者/读者索取更多资源

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 beta-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 beta-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.

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