Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in clopidogrel-treated Chinese patientsZhong- Ling Zhuo, Hai- Peng Xian, Yan Long, Chang Liu, Yuan- Yuan Sun, Yin- Ting Ma, Hua Gao, Jing- Zhong Zhao, Xiao- Tao Zhao
Department of Clinical Laboratory, Peking University Peoples Hospital; Beijing-China
Objective: To investigate the association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance (CR) in patients with cardiovascular disease in Beijing district.Keywords: CYP2C19, ABCB1 gene, polymorphism, clopidogrel resistance, adenosine diphosphate, induced platelet inhibition rate
Methods: In total, 325 patients were enrolled in the study, including 101 experimental group patients and 224 control group patients. The experimental group was divided into CR group (n=30) and non-CR group (n=71) according to the adenosine diphosphate (ADP)-induced platelet inhibition rate in thromboelastography (TEG) (ADP-induced platelet inhibition rate of <30% was defined as CR and rate of 30%100% was defined as non-CR). Genotypes, including CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*17, and ABCB1, were determined using time-of-flight mass spectrometry (Clin-TOF) and Sanger sequencing in all patients.
Results: In the experimental group, carriers of CYP2C19 heterozygous (*1/*2, n=46; *1/*3, n=7), and mutation homozygous (*2/*2, n=7; *2/*3, n=3; *3/*3, n=0) genotypes showed significantly lower ADP-induced platelet inhibition rates than noncarriers (*1/*1, n=38; p=0.035 and 0.001, respectively); the carriage of mutant CYP2C19*2 or *3 allele was significantly associated with an increased risk of CR. In contrast, carriers of ABCB1 heterozygous (TC, n=50) showed significantly lower ADP-induced platelet inhibition rates than noncarriers (CC, n=39, p=0.097), and there was no significant correlation between ABCB1 genotypes and higher CR risk.
Conclusion: The carriage of CYP2C19*2 or *3 mutant allele was significantly associated with attenuated platelet response to clopidogrel and increased CR risk. The carriage of ABCB1 mutant allele was not significantly associated with CR risk.
Zhong- Ling Zhuo, Hai- Peng Xian, Yan Long, Chang Liu, Yuan- Yuan Sun, Yin- Ting Ma, Hua Gao, Jing- Zhong Zhao, Xiao- Tao Zhao. Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in clopidogrel-treated Chinese patients. Anatol J Cardiol. 2018; 19(2): 123-129
Sorumlu Yazar: Xiao- Tao Zhao, China