title: Genotype Frequencies of CYP2C19, P2Y12 and GPIIIa Polymorphisms in Coronary Heart Disease Patients of Han Ethnicity, and Their Impact on Clopidogrel Responsiveness.
abstract: To investigate the genotype frequencies of cytochrome P450, family2, subfamily C, polypeptide19 (CYP2C19); P2Y12 receptor; and glycoprotein IIIa polymorphisms in patients with coronary heart disease and their impact on clopidogrel responsiveness and major adverse cardiac events (MACEs).A total of 146 coronary heart disease patients of Han ethnicity, on a clopidogrel regimen, were enrolled. Polymerase chain reaction and DNA sequencing were used to detect the genotype and allelic frequencies of CYP2C19 ((*)2,(*)3,(*)17), P2Y12 (C34T, G52T, T744C) and GPIIIa (T1565C) polymorphisms. Clinical and laboratory data were compared between the high on-treatment platelet reactivity (HTPR) versus normal groups.HTPR was identified in 35 (24%) patients. CYP2C19(*)2 (G681A) polymorphism was found to be significantly associated with HTPR (P < 0.05). A allele frequencies were significantly higher in the HTPR group versus the normal group (P < 0.05). On logistic regression analysis, CYP2C19(*)2 (G681A) polymorphism was found to be an independent risk factor associated with HTPR. No link could be established between genetic polymorphisms and recurrence of MACEs, or between HTPR and recurrence of MACEs.The genetic polymorphisms in CYP2C19(*)2 were closely associated with HTPR. The frequency of the A allele of CYP2C19(*)2 was significantly associated with HTPR, with A allele carriers being more likely to develop HTPR.
authors.affiliation: Department of Cardiology, Guang-zhou Institute of Cardiovascular Diseases, The Second Affiliated Hospital of Guangzhou Medical University.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Ou
authors.forename: Yongcong
authors.initials: Y
authors.lastname: He
authors.forename: Aiqun
authors.initials: A
authors.lastname: Li
authors.forename: Benrong
authors.initials: B
authors.lastname: Liu
authors.forename: Lijun
authors.initials: L
authors.lastname: Jin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D002681:China; D000077144:Clopidogrel; D003327:Coronary Disease / Q000188:drug therapy / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C061248:ITGB3 protein, human; D039661:Integrin beta3; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine