AUTHOR=Chen Lida , Zheng Chao , Hao Mengmeng , Gao Peng , Zhao Meimei , Cao Yongtong , Ma Liang 

TITLE=Association of ABCC2 polymorphism with clopidogrel response in Chinese patients undergoing percutaneous coronary intervention

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.889473

DOI=10.3389/fphar.2022.889473

ISSN=1663-9812

ABSTRACT=<p><bold>Aim:</bold> In this study, we investigated the association between <italic>ABCC2</italic> polymorphism and clopidogrel response as well as the associated hypothetical mechanism.</p><p><bold>Methods:</bold> Chinese patients (213) with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) and received clopidogrel were recruited. Thereafter, their ADP-induced platelet inhibition rates (PAIR%) were determined <italic>via</italic> thromboelastometry. Further, the single-nucleotide polymorphisms (SNPs) of <italic>ABCC2</italic> were genotyped using high-resolution melting curve (HRM)-PCR, while <italic>CYP2C19</italic>*2 and *3 polymorphisms were genotyped <italic>via</italic> real-time PCR.</p><p><bold>Results:</bold> The allele frequencies of <italic>ABCC2</italic> rs717620 were 74.88 and 25.12% for the C and T alleles, respectively. Further, <italic>ABCC2</italic> rs717620 TT carriers exhibited significantly higher PAIR% values (72.60 ± 27.69) than both CT (61.44 ± 23.65) and CC carriers (52.72 ± 21.99) (<italic>p</italic> = 0.047 and <italic>p</italic> = 0.001, respectively), and <italic>ABCC2</italic> rs717620 CT carriers showed significantly higher mean PAIR% values than <italic>ABCC2</italic> rs717620 CC carriers (<italic>p</italic> = 0.011). However, the PAIR% values corresponding to <italic>ABCC2</italic> rs2273697 and <italic>ABCC2</italic> rs3740066 carriers were not different. Additionally, <italic>CYP2C19</italic>*2 AA carriers presented significantly lower PAIR% values than <italic>CYP2C19</italic>*2 GA (<italic>p</italic> = 0.015) and GG (<italic>p</italic> = 0.003) carriers, and <italic>CYP2C19</italic>*3 GA carriers also presented significantly lower PAIR% values than <italic>CYP2C19</italic>*3 GG carriers (<italic>p</italic> = 0.041). In patients with <italic>CYP2C19</italic> extensive metabolizers (EM), <italic>ABCC2</italic> rs717620 TT carriers showed significantly higher PAIR% values (89.77 ± 9.73) than CT (76.76 ± 26.00) and CC carriers (74.09 ± 25.29) (<italic>p</italic> = 0.040 and <italic>p</italic> = 0.009, respectively). In patients with <italic>CYP2C19</italic> poor metabolizers (PM), <italic>ABCC2</italic> rs717620 CC carriers showed significantly lower PAIR% values (51.72 ± 25.78) than CT carriers (75.37 ± 23.57) (<italic>p</italic> = 0.043). Furthermore, after adjusting for confounding factors, <italic>ABCC2</italic> rs717620 was identified as a strong predictor of clopidogrel hyperreactivity.</p><p><bold>Conclusion:</bold> We proposed a new target, <italic>ABCC2</italic> rs717620, in the efflux pathway that affects individual responses to clopidogrel. The TT allele of <italic>ABCC2</italic> rs717620 was also identified as an independent risk factor for clopidogrel hyperreactivity, and <italic>CYP2C19</italic>*2 and *3 showed association with an increased risk for clopidogrel resistance. Additionally, <italic>ABCC2</italic> rs717620 may affect individual responses to clopidogrel <italic>via</italic> post-transcriptional regulation and interaction with <italic>CYP2C19</italic>. These findings provide new insights that may guide the accurate use of clopidogrel.</p>