Association of genetic variant and platelet function in patients undergoing neuroendovascular stenting

Postgrad Med J. 2017 Sep;93(1103):555-559. doi: 10.1136/postgradmedj-2016-134745. Epub 2017 Mar 9.

Abstract

Introduction: The risk of recurrent ischaemic events is related to platelet function, which is often assessed by thromboelastography (TEG). TEG has high interindividual variability.

Objective: To identify causal variants associated with TEG parameters in patients who receive aspirin and clopidogrel after intra- or extracranial stenting.

Methods: Patients who underwent stenting for extracranial or intracranial stenosis (70-99%) were recruited into the study. Blood samples were obtained for TEG to assess the platelet function before stenting. Aspirin- and clopidogrel-related genetic polymorphisms were determined by the MassARRAY method. Minor allele frequency and Hardy-Weinberg equilibrium (HWE) tests and linkage disequilibrium (LD) analysis were carried out. The influences of genetic polymorphism on TEG parameters were analysed by linear regression.

Results: A total of 249 patients were included in this study. Twenty-two selected single nucleotide polymorphisms (SNPs) were genotyped, and no significant deviation from HWE was found for any SNP in the study patients. Four SNPs-rs2104543, rs12772169, rs1998591 and rs1042194-within CYP2C18 were in high LD, and the genetic polymorphisms had a significant impact on the TEG parameters maximal clot strength (MAThrombin) and ADP-induced platelet-fibrin clot strength (MAADP). Patients who carried the loss-of-function CYP2C19*2 (rs4244285) allele were also at risk of increased MAThrombin and MAADP.

Conclusions: Testing for these polymorphisms may be valuable in the identification of patients at high risk of recurrent ischaemic events. Alternative treatments may be considered for these high-risk patients.

Trial registration number: NCT01925872.

Keywords: CLINICAL PHARMACOLOGY; STROKE MEDICINE.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Aspirin / administration & dosage
  • Brain Ischemia / genetics*
  • Brain Ischemia / therapy*
  • Clopidogrel
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage
  • Polymorphism, Single Nucleotide*
  • Recurrence
  • Stents*
  • Stroke / genetics*
  • Stroke / therapy*
  • Thrombelastography
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT01925872