P2Y12 receptor gene polymorphism and antiplatelet effect of clopidogrel in patients with coronary artery disease after coronary stenting

被引:39
作者
Zoheir, Naguib [1 ]
Abd Elhamid, Samah [1 ]
Abulata, Nelly [1 ]
El Sobky, Mehry [2 ]
Khafagy, Doaa [1 ]
Mostafa, Amr [3 ]
机构
[1] Cairo Univ, Fac Med, Dept Clin Pathol, Cairo, Egypt
[2] Cairo Univ, Fac Med, Dept Clin Pathol, Res Inst Ophthalmol, Cairo, Egypt
[3] Cairo Univ, Fac Med, Dept Cardiol, Cairo, Egypt
关键词
acute coronary syndrome; clopidogrel; platelet aggregation; platelet polymorphism; SEQUENCE VARIATIONS; PLATELET RESPONSE; P2Y(12); ASSOCIATION; ADP;
D O I
10.1097/MBC.0b013e32835e98bf
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Platelets have a central role in the pathophysiology of thrombosis. Adenosine diphosphate (ADP) plays a pivotal role as an agonist of platelet activation. Genetic polymorphisms of the P2Y12 ADP receptor might influence the activation of this receptor by ADP or the response of patients to platelet inhibitors. The present study was conducted on a total number of 80 participants, 40 patients were diagnosed with acute coronary syndrome and 40 sex and aged-matched healthy volunteers were included as controls. Platelet aggregation was assessed (before and 1 week after clopidogrel administration) and genotyping of the T744C genetic polymorphism of P2Y12 receptor gene was carried out using the restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) method. Platelet aggregation of the patients had a range of 54-183% before clopidogrel administration and had a range of 4-113% after its administration. Genotyping of the candidate gene revealed that 72.5% of the patients had a wild allele (TT), whereas 27.5% had a C allele (heterozygous CT, homozygous CC). On the contrary, 97.5% of controls had a wild allele (TT), whereas 2.5% had a C allele (heterozygous CT, homozygous CC). Our study elicited an association between the T744C polymorphism of the P2Y12 ADP receptor gene and platelet reactivity. Carrying the C allele at this position is associated with an increased platelet activation response to ADP. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:525 / 531
页数:7
相关论文
共 18 条
[1]   Lack of association between the P2Y12 receptor gene polymorphism and platelet response to clopidogrel in patients with coronary artery disease [J].
Angiolillo, DJ ;
Fernandez-Ortiz, A ;
Bernardo, E ;
Ramírez, C ;
Cavallari, U ;
Trabetti, E ;
Sabaté, M ;
Jimenez-Quevedo, P ;
Hernández, R ;
Moreno, R ;
Escaned, J ;
Alfonso, F ;
Bañuelos, C ;
Costa, MA ;
Bass, TA ;
Pignatti, PF ;
Macaya, C .
THROMBOSIS RESEARCH, 2005, 116 (06) :491-497
[2]  
[Anonymous], 2006, J Am Coll Cardiol, V47, pe1e121, DOI DOI 10.1016/j.jacc.2005.12.001
[3]   The relevance of P2Y12-receptor gene variation for the outcome of clopidogrel-treated patients undergoing elective coronary stent implantation: A clinical follow-up [J].
Bouman, Heleen J. ;
van Werkum, Jochem W. ;
Rudez, Goran ;
Hackeng, Christian M. ;
Leebeek, Frank W. G. ;
ten Cate, Hugo ;
ten Berg, Jurrien M. ;
de Maat, Moniek P. M. .
THROMBOSIS AND HAEMOSTASIS, 2012, 107 (01) :189-191
[4]   Gene sequence variations of the platelet P2Y12 receptor are associated with coronary artery disease [J].
Cavallari, Ugo ;
Trabetti, Elisabetta ;
Malerba, Giovanni ;
Biscuola, Michele ;
Girelli, Domenico ;
Olivieri, Oliviero ;
Martinelli, Nicola ;
Angiolillo, Dominick J. ;
Corrocher, Roberto ;
Pignatti, Pier Franco .
BMC MEDICAL GENETICS, 2007, 8
[5]   Role of the T744C polymorphism of the P2Y12 gene on platelet response to a 600-mg loading dose of clopidogrel in 597 patients with non-ST-segment elevation acute coronary syndrome [J].
Cuisset, Thomas ;
Frere, Corinne ;
Quilici, Jacques ;
Morange, Pierre-Emmanuel ;
Saut, Noemie ;
Lambert, Marc ;
Camoin, Laurence ;
Vague, Irene Juhan ;
Bonnet, Jean-Louis ;
Alessi, Marie-Christine .
THROMBOSIS RESEARCH, 2007, 120 (06) :893-899
[6]   Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects [J].
Fontana, P ;
Dupont, A ;
Gandrille, S ;
Bachelot-Loza, C ;
Reny, JL ;
Aiach, M ;
Gaussem, P .
CIRCULATION, 2003, 108 (08) :989-995
[7]   Specific impairment of human platelet P2YAC ADP receptor-mediated signalling by the antiplatelet drug clopidogrel [J].
Geiger, J ;
Brich, J ;
Hönig-Liedl, P ;
Eigenthaler, M ;
Schanzenbächer, P ;
Herbert, JM ;
Walter, U .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1999, 19 (08) :2007-2011
[8]   Dimorphism in the P2Y1 ADP receptor gene is associated with increased platelet activation response to ADP [J].
Hetherington, SL ;
Singh, RK ;
Lodwick, D ;
Thompson, JR ;
Goodall, AH ;
Samani, NJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (01) :252-257
[9]   Platelet purinergic receptors [J].
Kunapuli, SP ;
Dorsam, RT ;
Kim, S ;
Quinton, TM .
CURRENT OPINION IN PHARMACOLOGY, 2003, 3 (02) :175-180
[10]   Identification of P2Y12 single-nucleotide polymorphisms and their influences on the variation in ADP-induced platelet aggregation [J].
Lee, Su-Jun ;
Jung, Il-Sun ;
Jung, Eun-Ji ;
Choi, Ji-Yeop ;
Yeo, Chang-Woo ;
Cho, Doo-Yeoun ;
Kim, Yang-Weon ;
Lee, Sang-Seop ;
Shin, Jae-Gook .
THROMBOSIS RESEARCH, 2011, 127 (03) :220-227