TY - JOUR
T1 - PTPRD gene associated with blood pressure response to atenolol and resistant hypertension
AU - Gong, Yan
AU - McDonough, Caitrin W.
AU - Beitelshees, Amber L.
AU - Rouby, Nihal El
AU - Hiltunen, Timo P.
AU - O'Connell, Jeffrey R.
AU - Padmanabhan, Sandosh
AU - Langaee, Taimour Y.
AU - Hall, Karen
AU - Schmidt, Siegfried O.F.
AU - Curry, Robert W.
AU - Gums, John G.
AU - Donner, Kati M.
AU - Kontula, Kimmo K.
AU - Bailey, Kent R.
AU - Boerwinkle, Eric
AU - Takahashi, Atsushi
AU - Tanaka, Toshihiro
AU - Kubo, Michiaki
AU - Chapman, Arlene B.
AU - Turner, Stephen T.
AU - Pepine, Carl J.
AU - Cooper-DeHoff, Rhonda M.
AU - Johnson, Julie A.
N1 - Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Atenolol
KW - Blood pressure response
KW - Genomewide association study
KW - PTPRD
KW - Pharmacogenomic evaluation of antihypertensive responses
KW - Pharmacogenomics
KW - Resistant hypertension
UR - https://www.scopus.com/pages/publications/84943159217
UR - https://www.scopus.com/pages/publications/84943159217#tab=citedBy
U2 - 10.1097/HJH.0000000000000714
DO - 10.1097/HJH.0000000000000714
M3 - Article
C2 - 26425837
AN - SCOPUS:84943159217
SN - 0263-6352
VL - 33
SP - 2278
EP - 2285
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 11
ER -