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

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

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.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Adult
  • African Continental Ancestry Group / genetics
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Atenolol / therapeutic use*
  • Blood Pressure / drug effects*
  • Blood Pressure / genetics*
  • Essential Hypertension
  • European Continental Ancestry Group / genetics
  • Female
  • Genome-Wide Association Study
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / genetics
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics*

Substances

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