Replicated evidence for aminoacylase 3 and nephrin gene variations to predict antihypertensive drug responses

Pharmacogenomics. 2017 Apr;18(5):445-458. doi: 10.2217/pgs-2016-0204. Epub 2017 Mar 29.

Abstract

Aim: To replicate the genome-wide associations of the antihypertensive effects of bisoprolol and losartan in GENRES, using the Finnish patients of LIFE study.

Patients & methods: We analyzed association of four SNPs with atenolol and three SNPs with losartan response in 927 Finnish LIFE patients (467 for atenolol and 460 for losartan).

Results: rs2514036, a variation at a transcription start site of ACY3, was associated with blood pressure response to atenolol in men in LIFE. Response to bisoprolol was correlated to baseline plasma levels of N-acetylphenylalanine and phenylalanine (ACY3 substrate and end product, respectively) in GENRES study. NPHS1 variation rs3814995 was associated with losartan effect in LIFE.

Conclusion: We provide support for two pharmacogenomic markers for beta-blockers and angiotensin receptor antagonists.

Keywords: aminoacylase 3; atenolol; bisoprolol; genome-wide; hypertension; losartan; nephrin; pharmacogenomics.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amidohydrolases / genetics*
  • Antihypertensive Agents / pharmacology*
  • Blood Pressure / drug effects*
  • Blood Pressure / genetics*
  • Cross-Over Studies
  • Double-Blind Method
  • Finland / epidemiology
  • Genetic Variation / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Predictive Value of Tests
  • Prospective Studies
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Membrane Proteins
  • nephrin
  • Amidohydrolases
  • aminoacylase III, rat