Identification of PEAR1 SNPs and their influences on the variation in prasugrel pharmacodynamics

Pharmacogenomics. 2013 Jul;14(10):1179-89. doi: 10.2217/pgs.13.108.

Abstract

Aim: The present study aimed to investigate PEAR1 genetic polymorphisms and pharmacogenetic variability in the pharmacodynamics of prasugrel, a new oral antiplatelet agent, in healthy Han Chinese subjects.

Patients & methods: The inhibition of adenosine diphosphate-induced platelet aggregation was measured pre- and post-administration using the VerifyNow(®) P2Y12 assay. The genetic sequence of PEAR1 exons and previously reported SNPs in the PEAR1 gene were investigated.

Results: A total of 28 variations were identified in PEAR1. The SNPs in two regions of the PEAR1 gene, from rs3737224 to rs822442, and from rs1214331 to rs12566888, probably play important roles in prasugrel pharmacodynamics.

Conclusion: Further studies with larger sample sizes are recommended to explore the clinical importance of PEAR1 SNPs in prasugrel and other antiplatelet therapies. Original submitted 18 December 2012; Revision submitted 26 April 2013.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / administration & dosage
  • Adult
  • Blood Platelets / drug effects
  • Blood Platelets / pathology
  • Female
  • Humans
  • Male
  • Pharmacogenetics*
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Platelet Aggregation / drug effects
  • Platelet Aggregation / genetics*
  • Polymorphism, Single Nucleotide
  • Prasugrel Hydrochloride
  • Receptors, Cell Surface / genetics*
  • Thiophenes / administration & dosage*
  • Thiophenes / adverse effects

Substances

  • PEAR1 protein, human
  • Piperazines
  • Receptors, Cell Surface
  • Thiophenes
  • Adenosine Diphosphate
  • Prasugrel Hydrochloride