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

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 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 and P = 5.9 × 10, 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). 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).

CONCLUSION:

PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.

• Authors: 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 Jr, 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
• Journal: Journal of hypertension (J Hypertens) Vol. 33 Issue 11 Pg. 2278-85 (Nov 2015) ISSN: 1473-5598 [Electronic] England
• PMID: 26425837 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Antihypertensive Agents
• Atenolol
• PTPRD protein, human
• Receptor-Like Protein Tyrosine Phosphatases, Class 2

Topics

• Adrenergic beta-Antagonists (therapeutic use)
• Adult
• Aged
• Antihypertensive Agents (therapeutic use)
• Atenolol (therapeutic use)
• Black People (genetics)
• Blood Pressure (drug effects, genetics)
• Essential Hypertension
• Female
• Genome-Wide Association Study
• Humans
• Hypertension (drug therapy, genetics)
• Male
• Middle Aged
• Pharmacogenetics
• Polymorphism, Single Nucleotide
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (genetics)
• White People (genetics)