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. Chapman; Stephen T. Turner; Carl J. Pepine; Rhonda M. Cooper-DeHoff; Julie A. Johnson

doi:10.1097/HJH.0000000000000714

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 journal › Article › peer-review

21 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 language	English (US)
Pages (from-to)	2278-2285
Number of pages	8
Journal	Journal of hypertension
Volume	33
Issue number	11
DOIs	https://doi.org/10.1097/HJH.0000000000000714
State	Published - 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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10.1097/HJH.0000000000000714

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Gong, Y., McDonough, C. W., Beitelshees, A. L., Rouby, N. E., Hiltunen, T. P., O'Connell, J. R., Padmanabhan, S., Langaee, T. Y., Hall, K., Schmidt, S. O. F., Curry, R. W., Gums, J. G., Donner, K. M., Kontula, K. K., Bailey, K. R., Boerwinkle, E., Takahashi, A., Tanaka, T., Kubo, M., ... Johnson, J. A. (2015). PTPRD gene associated with blood pressure response to atenolol and resistant hypertension. Journal of hypertension, 33(11), 2278-2285. https://doi.org/10.1097/HJH.0000000000000714

Gong, Y, McDonough, CW, Beitelshees, AL, Rouby, NE, Hiltunen, TP, O'Connell, JR, Padmanabhan, S, Langaee, TY, Hall, K, Schmidt, SOF, Curry, RW, Gums, JG, Donner, KM, Kontula, KK, Bailey, KR, Boerwinkle, E, Takahashi, A, Tanaka, T, Kubo, M, Chapman, AB, Turner, ST, Pepine, CJ, Cooper-DeHoff, RM & Johnson, JA 2015, 'PTPRD gene associated with blood pressure response to atenolol and resistant hypertension', Journal of hypertension, vol. 33, no. 11, pp. 2278-2285. https://doi.org/10.1097/HJH.0000000000000714

@article{d824f5d6d0b44b69bc93d6b318bce082,

title = "PTPRD gene associated with blood pressure response to atenolol and resistant hypertension",

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.",

keywords = "Atenolol, Blood pressure response, Genomewide association study, PTPRD, Pharmacogenomic evaluation of antihypertensive responses, Pharmacogenomics, Resistant hypertension",

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

year = "2015",

doi = "10.1097/HJH.0000000000000714",

language = "English (US)",

volume = "33",

pages = "2278--2285",

journal = "Journal of hypertension",

issn = "0263-6352",

publisher = "Lippincott Williams and Wilkins",

number = "11",

}

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.

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

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U2 - 10.1097/HJH.0000000000000714

DO - 10.1097/HJH.0000000000000714

M3 - Article

C2 - 26425837

AN - SCOPUS:84943159217

SN - 0263-6352

VL - 33

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EP - 2285

JO - Journal of hypertension

JF - Journal of hypertension

IS - 11

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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