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

被引：37

作者：

Gong, Yan ^{[1
,2
]}

McDonough, Caitrin W. ^{[1
,2
]}

Beitelshees, Amber L. ^{[3
,4
]}

El Rouby, Nihal ^{[1
,2
]}

Hiltunen, Timo P. ^{[5
,6
]}

O'Connell, Jeffrey R. ^{[3
,4
]}

Padmanabhan, Sandosh ^{[7
]}

Langaee, Taimour Y. ^{[1
,2
]}

Hall, Karen

Schmidt, Siegfried O. F. ^{[8
]}

Curry, Robert W., Jr. ^{[8
]}

Gums, John G. ^{[1
,2
,8
]}

Donner, Kati M. ^{[9
]}

Kontula, Kimmo K. ^{[5
,6
]}

Bailey, Kent R. ^{[10
]}

Boerwinkle, Eric ^{[11
]}

Takahashi, Atsushi ^{[12
]}

Tanaka, Toshihiro ^{[12
]}

Kubo, Michiaki ^{[12
]}

Chapman, Arlene B. ^{[13
]}

Turner, Stephen T. ^{[10
]}

Pepine, Carl J. ^{[14
]}

Cooper-DeHoff, Rhonda M. ^{[1
,2
,14
]}

Johnson, Julie A. ^{[1
,2
,14
]}

机构：

[1] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA

[2] Univ Florida, Ctr Pharmacogen, Gainesville, FL 32610 USA

[3] Univ Maryland, Dept Med, Baltimore, MD 21201 USA

[4] Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA

[5] Univ Helsinki, Dept Med, Helsinki, Finland

[6] Univ Cent Hosp Helsinki, Helsinki, Finland

[7] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland

[8] Univ Florida, Coll Med, Dept Community Hlth & Family Med, Gainesville, FL 32610 USA

[9] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland

[10] Mayo Clin, Coll Med, Rochester, MN USA

[11] Univ Texas Houston, Ctr Human Genet, Houston, TX USA

[12] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan

[13] Emory Univ, Sch Med, Atlanta, GA USA

[14] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32610 USA

来源：

JOURNAL OF HYPERTENSION | 2015年 / 33卷 / 11期

关键词：

atenolol; blood pressure response; genome-wide association study; pharmacogenomic evaluation of antihypertensive responses; pharmacogenomics; PTPRD; resistant hypertension; GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; GLOBAL BURDEN; PREDICTORS; IDENTIFY;

D O I：

10.1097/HJH.0000000000000714

中图分类号：

R6 [外科学];

学科分类号：

1002 ; 100210 ;

摘要：

Objective: The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the -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=3.2x10(-6) and P=5.9x10(-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=8.25x10(-6)). rs12346562 had a similar trend in association with response to bisoprolol (a different -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=3.2x10(-5)).Conclusion: PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.

引用

页码：2278 / 2285

页数：8

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