Hypertension Susceptibility Loci and Blood Pressure Response to Antihypertensives

Author:

Gong Yan1,McDonough Caitrin W.1,Wang Zhiying1,Hou Wei1,Cooper-DeHoff Rhonda M.1,Langaee Taimour Y.1,Beitelshees Amber L.1,Chapman Arlene B.1,Gums John G.1,Bailey Kent R.1,Boerwinkle Eric1,Turner Stephen T.1,Johnson Julie A.1

Affiliation:

1. From the Department of Pharmacotherapy and Translational Research (Y.G., C.W.M., R.M.C.-D., T.Y.L., J.G.G., J.A.J.), Department of Biostatistics, College of Medicine (W.H.), Division of Cardiovascular Medicine, College of Medicine (R.M.C.-D., J.A.J.), and Department of Community Health and Family Medicine (J.G.G.), University of Florida, Gainesville, FL; Division of Epidemiology, University of Texas at Houston, Houston, TX (Z.W., E.B.); Division of Endocrinology, Diabetes and Nutrition, University...

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 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Genetics (clinical),Cardiology and Cardiovascular Medicine,Genetics

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