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Efffect of the ABCC 3 –211 C/T polymorphism on clopidogrel responsiveness in patients with percutaneous coronary intervention
Author(s) -
Zou JianJun,
Fan HongWei,
Chen ShaoLiang,
Tan Jie,
He BangShun,
Xie HongGuang
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12118
Subject(s) - clopidogrel , genotype , medicine , percutaneous coronary intervention , genotyping , pharmacology , platelet , pharmacogenetics , gastroenterology , gene , chemistry , biochemistry , aspirin , myocardial infarction
Summary Multidrug resistance protein 3 ( MPR3 ), encoded by the ATP ‐binding cassette, subfamily C ( CFTR / MRP ), member 3 ( ABCC 3 ) gene, functions as an important drug efflux transporter. The ABCC 3 –211 C / T polymorphism is associated with decreased MRP 3 mRNA expression, and low MRP 3 mRNA expression is associated with increased clopidogrel response in patients. The aim of the present study was to determine whether the –211 C / T polymorphism is associated with altered antiplatelet effects and clinical outcomes in clopidogrel‐treated patients. A subcohort of 249 patients not carrying the CYP 2C19 * 2 , * 3 or * 17 variant was identified from a total of 617 consecutive clopidogrel‐treated patients undergoing percutaneous coronary intervention and then categorized into three groups on the basis of their ABCC 3 –211 C / T genotype. Baseline data, clinical characteristics and DNA samples were collected for all patients. Light transmittance aggregometry was used to determine ADP ‐induced maximum platelet aggregation ( MPA ) in blood samples obtained from patients on Day 3 after starting daily clopidogrel maintenance doses. Genotyping of CYP 2C19 * 2 , * 3 and * 17 variants and the ABCC 3 –211 C / T polymorphism was performed using matrix‐assisted laser desorption ionization time‐of‐flight ( MALDI ‐ TOF ) mass spectrometry. The primary clinical end‐point was a definite stent thrombosis ( ST ) episode, whereas secondary end‐points were other major adverse cardiovascular events within 12 months after stenting. There were no differences in MPA values according to ABCC 3 –211 C / T genotype. A multiple linear regression model revealed that the ABCC 3 –211 C / T polymorphism was not independently associated with ADP ‐induced MPA measurements; a multiple logistic regression model revealed that carrying the ABCC 3 –211 C allele was not associated with the risk of developing an ST event in clopidogrel‐treated patients not harbouring CYP 2C19 * 2 , * 3 and * 17 variants. In conclusion, the ABCC 3 –211 C / T polymorphism seems not to be associated with altered antiplatelet effects and clinical outcomes in clopidogrel‐treated patients.