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

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.