PTPRD gene associated with blood pressure response to atenolol and resistant hypertension

• Type of Material: Article
• Authors: Yan Gong, University of Florida; Caitrin W. McDonough, University of Florida; Amber L. Beitelshees, University of Maryland; Nihal El Rouby, University of Florida; Timo P. Hiltunen, University of Helsinki; Jeffrey R. O'Connell, University of Maryland; Sandosh Padmanabhan, University of Glasgow; Taimour Y. Langaee, University of Florida; Karen Hall, University of Florida; Siegfried O.F. Schmidt, University of Florida; Robert W. Curry, University of Florida; John G. Gums, University of Florida; Kati M. Donner, University of Helsinki; Kimmo K. Kontula, University of Helsinki; Kent R. Bailey, Mayo Clinic; Eric Boerwinkle, University of Texas at Houston; Atsushi Takahashi, RIKEN; Toshihiro Tanaka, RIKEN; Michiaki Kubo, RIKEN; Arlene Chapman, Emory University; Stephen T. Turner, Mayo Clinic; Carl J. Pepine, University of Florida; Rhonda M. Cooper-DeHoff, University of Florida; Julie A. Johnson, University of Florida
• Language: English
• Date: 2015-11-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/HJH.0000000000000714
• Title of Journal or Parent Work: Journal of Hypertension
• ISSN: 0263-6352
• Volume: 33
• Issue: 11
• Start Page: 2278
• End Page: 2285
• Keywords: Science & Technology; blood pressure response; GLOBAL BURDEN; Cardiovascular System & Cardiology; CORONARY-ARTERY-DISEASE; genome-wide association study; TRIAL; Peripheral Vascular Disease; atenolol; pharmacogenomics; PTPRD; pharmacogenomic evaluation of antihypertensive responses; resistant hypertension; IDENTIFY; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pharmacology; Biology, Genetics

Abstract

Objective: The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-blocker atenolol. Methods: Genome-wide association analysis of BP response to atenolol monotherapy was performed in 233 white participants with uncomplicated hypertension in the pharmacogenomic evaluation of antihypertensive responses study. Forty-two polymorphisms with P less than 10−5 for association with either diastolic or systolic response to atenolol monotherapy were validated in four independent groups of hypertensive individuals (total n = 2114). Results: In whites, two polymorphisms near the gene PTPRD (rs12346562 and rs1104514) were associated with DBP response to atenolol (P = 3.2 × 10−6 and P = 5.9 × 10−6, respectively) with directionally opposite association for response to hydrochlorothiazide in another group of 228 whites (P = 0.0018 and P = 0.00012). A different polymorphism (rs10739150) near PTPRD was associated with response to atenolol in 150 black hypertensive individuals (P = 8.25 ×10−6). rs12346562 had a similar trend in association with response to bisoprolol (a different β-blocker) in 207 Finnish men in the genetics of drug responsiveness in essential hypertension study. In addition, an intronic single-nucleotide polymorphism (rs4742610) in the PTPRD gene was associated with resistant hypertension in whites and Hispanics in the international verapamil SR trandolapril study (meta-analysis P = 3.2 × 10−5). Conclusion: PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.