[Association of CYP2C19 gene polymorphisms with long-term recurrent risk of ischemic stroke among ethnic Han Chinese from Fujian]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2015 Dec;32(6):871-6. doi: 10.3760/cma.j.issn.1003-9406.2015.06.026.
[Article in Chinese]

Abstract

Objective: To assess the association of genetic polymorphisms of CYP2C19*2,*3,*17 with the recurrence risk of ischemic stroke during clopidogrel prevention in ethnic Han Chinese from Fujian Province.

Methods: Clinical data of 985 patients with acute ischemic stroke was collected. After 1 year postdischarge follow-up evaluations, only 114 patients with persistence of clopidogrel were enrolled. CYP2C19 genetic polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and direct sequencing ,then we analysis the correlation between polymorphisms and the recurrence of stroke.

Results: Among the 114 patients, 23 had a second onset whilst receiving clopidogrel treatment. During the antiplatelet therapy with clopidogrel, carriers of CYP2C19 poor metabolizer (CYP2C19*2/*2 or *2/*3) had a higher rate of recurrent stroke compared with extensive metabolizers (CYP2C19*1/*1) (OR=4.71, 95%CI: 1.18-18.80, P<0.05). Carriers of CYP2C19 *2 mutant allele had increased recurrence compared with those carrying none loss-of-function allele (OR=2.31, 95%CI: 1.20-4.46, P<0.05). The rate of recurrent stroke in those carrying homozygous mutant *2 allele (CYP2C19*2/*2) was 6.14 times greater than the rate of wild-type homozygotes (CYP2C19*1/*1) (95%CI: 1.54-24.54, P<0.05). Patients with previous stroke history had increased risk of recurrence (OR= 4.146, 95%CI: 1.259-13.655, P<0.05). However, CYP2C19*17 was not detected in the group.

Conclusion: For ethnic Han Chinese patients receiving clopidogrel treatment, carriers of poor metabolizer or homozygous mutant *2 allele (CYP2C19*2/*2) have a higher risk of recurrent stroke. The CYP2C19 *2 allele is an independent risk factor for recurrent stroke. Those with previous history of stroke are more prone to the recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Asians / genetics
  • Brain Ischemia / complications
  • Brain Ischemia / ethnology
  • China
  • Clopidogrel
  • Cytochrome P-450 CYP2C19 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide*
  • Recurrence
  • Risk Factors
  • Sequence Analysis, DNA
  • Stroke / ethnology
  • Stroke / etiology
  • Stroke / genetics*
  • Stroke / prevention & control
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Time Factors

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine