Details

Autor(en) / Beteiligte

• Liu, Rui
• Zhou, Zi-Yi
• Chen, Yi-Bei
• Li, Jia-Li
• Yu, Wei-Bang
• Chen, Xin-Meng
• Zhao, Min
• Zhao, Yuan-Qi
• Cai, Ye-Feng
• Jin, Jing
• Huang, Min

Titel

Associations of CYP3A4, NR1I2, CYP2C19 and P2RY12 polymorphisms with clopidogrel resistance in Chinese patients with ischemic stroke

Ist Teil von

• Acta pharmacologica Sinica, 2016-07, Vol.37 (7), p.882-888

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Aim： There is a high incidence of the antiplatelet drug clopidogrel resistance （OR） in Asian populations. Because clopidogrel is a prodrug, polymorphisms of genes encoding the enzymes involved in its biotransformation may be the primary influential factors. The goal of this study was to investigate the associations of polymorphisms of CYP3A4, NRll2, CYP2C19 and P2RY12 genes with CR in Chinese patients with ischemic stroke. Methods： A total of 191 patients with ischemic stroke were enrolled. The patients were treated with clopidogrel for at least 5 days. Platelet function was measured by light transmission aggregometry. The SNPs NRll2 （rs13059232）, CYP3A4＊IG （rs2242480）, CYP2C19＊2 （rs4244285） and P2RY12 （rs2046934） were genotyped. Results： The CR rate in this population was 36%. The CYP2C19＊2 variant was a risk factor for CR （＊2/＊2＋wt/＊2 vs wt/wt, OR： 2.366 95% CI： 1.180-4.741, P=0.014）, whereas the CYP3A4＊IG variant had a protective effect on CR （＊1/＊1 vs ＊1G/＊IG＋＊1/＊IG, OR： 2.360, 95% CI： 1.247-4.468, P=0.008）. The NRll2 （rs13059232） polymorphism was moderately associated with CR （CC vs TT＋TC, OR： 0.533, 95% CI： 0.286-0.991, P=0.046）. The C allele in P2RY12 （rs2046934） was predicted to be a protective factor for CR （CC＋TC vs TT, OR： 0.407, 95% CI： 0.191-0.867, P=O.O18）. In addition, an association was found between hypertension and CR （P=0.022）. Conclusion： The individuals with both the CYP2C19＊2 allele and hypertension are at high risk of CR during anti-thrombosis therapy. The CYP3A4＊IG allele, P2RY12 （rs2046934） C allele and NRll2 （rs13059232） CC genotype may be protective factors for CR. The associated SNPs studied may be useful to predict clopidogrel resistance in Chinese patients with ischemic stroke.