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

Yan Gong, Caitrin W. McDonough, Amber L. Beitelshees, Nihal El Rouby, Timo P. Hiltunen, Jeffrey R. O'Connell, Sandosh Padmanabhan, Taimour Y. Langaee, Karen Hall, Siegfried O.F. Schmidt, Robert W. Curry, John G. Gums, Kati M. Donner, Kimmo K. Kontula, Kent R. Bailey, Eric Boerwinkle, Atsushi Takahashi, Toshihiro Tanaka, Michiaki Kubo, Arlene B. ChapmanStephen T. Turner, Carl J. Pepine, Rhonda M. Cooper-DeHoff, Julie A. Johnson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Objective: The aim of this study is to identify singlenucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the b-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=8.2510-6). rs12346562 had a similar trend in association with response to bisoprolol (a different b-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=3.210-5). Conclusion: PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.

Original languageEnglish (US)
Pages (from-to)2278-2285
Number of pages8
JournalJournal of hypertension
Volume33
Issue number11
DOIs
StatePublished - 2015

Keywords

  • Atenolol
  • Blood pressure response
  • Genomewide association study
  • PTPRD
  • Pharmacogenomic evaluation of antihypertensive responses
  • Pharmacogenomics
  • Resistant hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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