title: Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome.
abstract: Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing percutaneous coronary intervention treated with clopidogrel were enrolled from September 2012 to June 2013. Residual platelet aggregations for all patients were measured by the Verify Now P2Y12 system. Sixteen single-nucleotide polymorphisms among nine genes were genotyped including CYP2C19, ABCB1 and PON1. In this study, CYP2C19*2 and CYP2C19*17 were strongly associated with higher platelet aggregation and lower platelet aggregation to clopidogrel treatment, respectively (P <0.001). Patients with CYP2C19*2 allele had a higher risk of high on-treatment platelet reactivity than non carriers (adjusted OR, 5.434; 95% CI, 1.918-15.399, P =0.01). The coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and the coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were also associated with poor response to clopidogrel. No significant relation of CYP2C19*3 and other polymorphisms to the platelet aggregation was found. In conclusion, CYP2C19*2, CYP2C19*17 coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were identified to be associated with response to clopidogrel treatment in Chinese Han patients.
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology,and School of Life Sciences, Fudan University, Shanghai 200433, People's Republic of China.lxb70@hotmail.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Yan
authors.initials: Y
authors.lastname: Lai
authors.forename: Yian
authors.initials: Y
authors.lastname: Yao
authors.forename: Jimin
authors.initials: J
authors.lastname: Li
authors.forename: Yunkai
authors.initials: Y
authors.lastname: Wang
authors.forename: S Lilly
authors.initials: SL
authors.lastname: Zheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Xuebo
authors.initials: X
authors.lastname: Liu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics; D044466:Asian People; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D000077144:Clopidogrel; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010597:Pharmacogenetics; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; C585599:CYP2B6 protein, human; C045793:CYP2C19 protein, human; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D013988:Ticlopidine