807 C/T polymorphism of the glycoprotein la gene and pharmacogenetic modulation of platelet response to dual antiplatelet treatment

被引:47
作者
Angiolillo, DJ
Fernandez-Ortiz, A
Bernardo, E
Ramírez, C
Escaned, J
Moreno, R
Hernández-Antolin, R
Sabaté, M
Trabetti, E
Pignatti, PF
Macaya, C
机构
[1] San Carlos Univ Hosp, Cardiovasc Inst, Intervent Cardiol Unit, E-28040 Madrid, Spain
[2] Univ Verona, Dept Mother & Child & Biol, I-37100 Verona, Italy
关键词
clopidogrel; glycoprotein la gene polymorphism; collagen; stent;
D O I
10.1097/01.mbc.0000114439.81125.86
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 la 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 la 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. (C) 2004 Lippincott Williams Wilkins.
引用
收藏
页码:427 / 433
页数:7
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