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J Hypertens. 2015 Nov;33(11):2278-85. doi: 10.1097/HJH.0000000000000714.

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

Author information

1
aDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida USA bDepartment of Medicine and Program in Personalized and Genomic Medicine, University of Maryland, Baltimore, Maryland, USA cDepartment of Medicine, University of Helsinki, and University Central Hospital of Helsinki, Helsinki, Finland dBHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK eDepartment of Community Health and Family Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA fInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. gCollege of Medicine, Mayo Clinic Rochester, Rochester, Minnesota USA hCenter for Human Genetics, University of Texas at Houston, Houston, Texas, USA iRIKEN Center for Integrative Medical Sciences, Yokohama, Japan jSchool of Medicine, Emory University, Atlanta, Georgia, USA kDivision of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.

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.

PMID:
26425837
PMCID:
PMC4788379
DOI:
10.1097/HJH.0000000000000714
[Indexed for MEDLINE]
Free PMC Article

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