PTPRD gene associated with blood pressure response to atenolol and resistant hypertension. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Gong, Yan; McDonough, Caitrin W.; Beitelshees, Amber L.; Rouby, Nihal El; Hiltunen, Timo P.; O'Connell, Jeffrey R.; Padmanabhan, Sandosh; Langaee, Taimour Y.; Hall, Karen; Schmidt, Siegfried O.F.; Curry, Robert W.; Gums, John G.; Donner, Kati M.; Kontula, Kimmo K.; Bailey, Kent R.; Boerwinkle, Eric; Takahashi, Atsushi; Tanaka, Toshihiro; Kubo, Michiaki; Chapman, Arlene B.; Turner, Stephen T.; Pepine, Carl J.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.
• Is Part Of: Journal of hypertension. Volume 33:Issue 11(2015:Nov.)
• Publication Date: 2015-11
• Subjects: atenolol -- blood pressure response -- genome-wide association study -- pharmacogenomic evaluation of antihypertensive responses -- pharmacogenomics -- PTPRD -- resistant hypertension; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000000714
• Languages: English
• ISSNs: 1473-5598

Abstract

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. Abstract : Supplemental Digital Content is available in the text