Hypertension susceptibility loci and blood pressure response to antihypertensives: Results from the pharmacogenomic evaluation of antihypertensive responses study

Yan Gong, Caitrin W. McDonough, Zhiying Wang, Wei Hou, Rhonda M. Cooper-DeHoff, Taimour Y. Langaee, Amber L. Beitelshees, Arlene B. Chapman, John G. Gums, Kent R. Bailey, Eric Boerwinkle, Stephen T. Turner, Julie A. Johnson

Research output: Contribution to journalReview article

39 Scopus citations

Abstract

Background-To date, 39 single nucleotide polymorphisms (SNPs) have been associated with blood pressure (BP) or hypertension in genome-wide association studies in whites. Our hypothesis is that the loci/SNPs associated with BP/hypertension are also associated with BP response to antihypertensive drugs. Methods and Results-We assessed the association of these loci with BP response to atenolol or hydrochlorothiazide monotherapy in 768 hypertensive participants in the Pharmacogenomics Responses of Antihypertensive Responses study. Linear regression analysis was performed on whites for each SNP in an additive model adjusting for baseline BP, age, sex, and principal components for ancestry. Genetic scores were constructed to include SNPs with nominal associations, and empirical P values were determined by permutation test. Genotypes of 37 loci were obtained from Illumina 50K cardiovascular or Omni1M genome-wide association study chips. In whites, no SNPs reached Bonferroni-corrected a of 0.0014, 6 reached nominal significance (P<0.05), and 3 were associated with atenolol BP response at P<0.01. The genetic score of the atenolol BP-lowering alleles was associated with response to atenolol (P=3.3×10-6 for systolic BP; P=1.6×10-6 for diastolic BP). The genetic score of the hydrochlorothiazide BP-lowering alleles was associated with response to hydrochlorothiazide (P=0.0006 for systolic BP; P=0.0003 for diastolic BP). Both risk score P values were <0.01 based on the empirical distribution from the permutation test. Conclusions-These findings suggest that selected signals from hypertension genome-wide association studies may predict BP response to atenolol and hydrochlorothiazide when assessed through risk scoring.

Original languageEnglish (US)
Pages (from-to)686-691
Number of pages6
JournalCirculation: Cardiovascular Genetics
Volume5
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Blood pressure
  • Diuretics
  • Hypertension
  • Pharmacogenetics
  • Polymorphisms
  • β-blocker

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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    Gong, Y., McDonough, C. W., Wang, Z., Hou, W., Cooper-DeHoff, R. M., Langaee, T. Y., Beitelshees, A. L., Chapman, A. B., Gums, J. G., Bailey, K. R., Boerwinkle, E., Turner, S. T., & Johnson, J. A. (2012). Hypertension susceptibility loci and blood pressure response to antihypertensives: Results from the pharmacogenomic evaluation of antihypertensive responses study. Circulation: Cardiovascular Genetics, 5(6), 686-691. https://doi.org/10.1161/CIRCGENETICS.112.964080