title: Hypertension susceptibility loci and blood pressure response to antihypertensives: results from the pharmacogenomic evaluation of antihypertensive responses study.
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.
  
  
  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 α 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. Clinical Trial Registration Information- clinicaltrials.gov; Identifier: NCT00246519.
authors.affiliation: Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, 32610, USA. gong@cop.ufl.edu
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Caitrin W
authors.initials: CW
authors.lastname: McDonough
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Hou
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: Amber L
authors.initials: AL
authors.lastname: Beitelshees
authors.forename: Arlene B
authors.initials: AB
authors.lastname: Chapman
authors.forename: John G
authors.initials: JG
authors.lastname: Gums
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use; D044383:Black People / Q000235:genetics; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D001262:Atenolol