title: 807 C/T Polymorphism of the glycoprotein Ia gene and pharmacogenetic modulation of platelet response to dual antiplatelet treatment.
abstract: Glycoprotein (GP) Ia/IIa is a major platelet-collagen receptor playing a key role in thrombosis following collagen exposure. The 807 C/T polymorphism of the GP Ia gene (ITGA2) has been associated with platelet GP Ia/IIa receptor expression, having T-allele carriers, increased receptor density and thrombotic risk. The aim of the study was to assess the role of the 807 C/T polymorphism on modulating platelet function in patients undergoing coronary stenting receiving a 300 mg clopidogrel loading dose. Platelet aggregation was assessed in 44 patients by light transmittance aggregometry following adenosine diphosphate and collagen stimuli at baseline, and 10 min, 4 h and 24 h after clopidogrel front loading. The T allele was found in 73% of patients. Clopidogrel reduced adenosine diphosphate-induced platelet aggregation (P < 0.01), which was similar in carriers and non-carriers of the T allele throughout the study (P = 0.73). Clopidogrel reduced collagen-induced platelet aggregation only in non-carriers of the T allele (P = 0.03), which resulted in an increase in T allele carriers during the overall study (P = 0.04). In conclusion, the T allele of the GP Ia gene modulates platelet aggregation and clopidogrel antiplatelet effects, suggesting an enhanced reactivity to fibrillar collagens (exposed during coronary stenting) in T allele carriers and might contribute to an increased thrombotic risk in these patients.
authors.affiliation: Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain. dominickjangiolillo@hotmail.com
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernandez-Ortiz
authors.forename: Esther
authors.initials: E
authors.lastname: Bernardo
authors.forename: Celia
authors.initials: C
authors.lastname: Ramírez
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.forename: Raul
authors.initials: R
authors.lastname: Moreno
authors.forename: Rosana
authors.initials: R
authors.lastname: Hernández-Antolin
authors.forename: Manel
authors.initials: M
authors.lastname: Sabaté
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trabetti
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D000077144:Clopidogrel; D003094:Collagen / Q000378:metabolism; D003327:Coronary Disease / Q000601:surgery; D005260:Female; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011110:Polymorphism, Genetic; D015607:Stents / Q000009:adverse effects; D013927:Thrombosis / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D039421:Integrin alpha2; D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine