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Association of genetic variant and platelet function in patients undergoing neuroendovascular stenting
  1. Xin-Gang Li1,2,
  2. Ning Ma3,
  3. Shu-Sen Sun4,
  4. Zhe Xu2,
  5. Wei Li2,
  6. Yong-Jun Wang2,
  7. Xin Yang5,
  8. Zhong-Rong Miao3,
  9. Zhi-Gang Zhao1,2
  1. 1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  2. 2Precision Medicine Research Center for Neurological Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  3. 3Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  4. 4College of Pharmacy, Western New England University, Springfield, Massachusetts, USA
  5. 5Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  1. Correspondence to Dr Zhong-Rong Miao, Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Dongcheng District, Beijing 100050, China; zhongrongm{at}163.com

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

  • CLINICAL PHARMACOLOGY
  • STROKE MEDICINE

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Footnotes

  • X-GL, NM and S-SS contributed equally.

  • Contributors X-GL: wrote the manuscript and analysed the data. NM: supervised the quality of the study and performed the experiments. S-SS: revised the manuscript. XY and ZX: analysed the data. WL, Y-JW, Z-RM and Z-GZ: conceived and designed the experiments.

  • Funding This work was supported by National Natural Science Foundation of China (81503157 and 81371290), Organization Department of Beijing Municipal Committee (2014000021469G258) and Capital Medical University (16JL72).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Beijing Tiantan Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement For access to the raw data and images obtained in this study, please contact the corresponding author.

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