Abstract | AIMS: METHODS: A total of 375 consecutive IS patients were genotyped for eight CYP SNPs using mass spectrometry. Platelet aggregation activity was measured before and after the 7-10 day treatment. Gene-gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients received clopidogrel therapy and were followed up for six months. Primary outcomes were evaluated as a composite of recurrent ischemic stroke (RIS), MI, and death. The secondary outcome was the modified Rankin Scale (mRS). RESULTS:
Clopidogrel resistance occurred in 153 patients (40.8%). The frequency of CYP3A5 (rs776746) GG/AG and CYP2C19*2 (rs4244285) AA/AG genotypes was significantly higher in clopidogrel-resistant patients than in sensitive patients. There was a significant gene-gene interaction between CYP3A5 (rs776746) and CYP2C19*2 (rs4244285). CYP2C19*2 AA and its interaction with CYP3A5 GG were independent predictors of clopidogrel resistance and affected the activity of platelet aggregation. Diabetes mellitus, CYP2C19*2 (rs4244285), clopidogrel resistance, and the interaction of CYP2C19*2 with CYP3A5 were all independent risk factors for the primary outcomes of clopidogrel treatment. Clopidogrel-resistant patients were more likely to have poor outcomes (mRS >2 points) compared with clopidogrel-sensitive patients. CONCLUSION: CYP SNPs and their interactions are associated with drug resistance and outcomes in acute IS patients.
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Authors | Xingyang Yi, Jing Lin, Yanfen Wang, Qiang Zhou, Chun Wang, Wen Cheng, Lifen Chi |
Journal | Journal of atherosclerosis and thrombosis
(J Atheroscler Thromb)
Vol. 23
Issue 10
Pg. 1188-1200
(Oct 01 2016)
ISSN: 1880-3873 [Electronic] Japan |
PMID | 26961113
(Publication Type: Journal Article)
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Chemical References |
- Platelet Aggregation Inhibitors
- Clopidogrel
- CYP2C19 protein, human
- Cytochrome P-450 CYP2C19
- Cytochrome P-450 CYP3A
- Ticlopidine
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Topics |
- Aged
- Clopidogrel
- Cytochrome P-450 CYP2C19
(genetics)
- Cytochrome P-450 CYP3A
(genetics)
- Female
- Humans
- Ischemia
(drug therapy, genetics)
- Male
- Middle Aged
- Platelet Aggregation Inhibitors
(pharmacology)
- Platelet Function Tests
- Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
(genetics)
- Prospective Studies
- Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
- Stroke
(drug therapy, genetics)
- Ticlopidine
(analogs & derivatives, pharmacology)
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