title: CES1A -816C as a genetic marker to predict greater platelet clopidogrel response in patients with percutaneous coronary intervention.
abstract: This study was designed to determine whether CES1A -816A/C polymorphism could be associated with altered clopidogrel response. Recruited patients were pretreated with 300 mg clopidogrel loading dose before undergoing percutaneous coronary intervention for stenting and genotyped with CYP2C19 *2, *3, or *17, and CES1A -816A/C, respectively. Adenosine diphosphate-induced maximum platelet aggregation (MPA) was determined on day 3 after initiation of daily clopidogrel maintenance doses. The clinical primary end point was the 1-year incidence of definite stent thrombosis (ST). Multivariable linear regression revealed that the CES1A -816A/C polymorphism was independently associated with MPA measures with an absolute β value of 6.76. Of 617 patients, a subcohort of 249 patients not carrying CYP2C19 *2, *3, or *17 were categorized into 3 groups based on the -816A/C genotype. The median MPA value was lower in 125 carriers of the -816C variant than in 124 noncarriers (21.5% vs. 31.7%, P = 0.001). The 1-year definite ST occurred in 7 patients in that subcohort, and only 1 ST case was one of carriers of the -816 A/A that was associated with higher MPA values. The CES1A -816C would be used to predict greater platelet response to clopidogrel than the CES1A -816A in percutaneous coronary intervention-treated patients not carrying CYP2C19 variants.
authors: *Division of Clinical Pharmacology, General Clinical Research Center; †Division of Cardiovascular Medicine, Department of Medicine, Nanjing Heart Center; and ‡Central Laboratory, General Clinical Research Center, Nanjing Medical University Nanjing First Hospital, Nanjing, China; and §Department of Pharmacology, Nanjing Medical University School of Pharmacy, Nanjing, China.
authors: Jian-Jun
authors: JJ
authors: Zou
authors: Shao-Liang
authors: SL
authors: Chen
authors: Hong-Wei
authors: HW
authors: Fan
authors: Jie
authors: J
authors: Tan
authors: Bang-Shun
authors: BS
authors: He
authors: Hong-Guang
authors: HG
authors: Xie
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005819:Genetic Markers; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine