The Association Between ABCB1Gene Polymorphism With The Clopidogrel Resistance

Dual antiplatelet therapy (Asprin and Clopidogrel) is the cornerstone toprevent the occurrence of thrombotic events after acute coronary syndrome(ACS)and percutaneous coronary intervention(PCI). However, individuals may vary inthe responses to clopidogrel. Patients after receiving standard clopidogrel therapystill are at the risk of subsequent death and ischemic events,which definded asclopidogrel resistanse(CR). The mechanisms of CR have not been fullyelucidated and are most probably multifactorial, and genetic factors play animportant role in CR. Clopidogrel is a prodrug that requires absorption inintestinal and biotransformation in liver to an active metabolite. ATP-bindingcassette subfamily B member1(ABCB1) plays an important part in theabsorption of clopidogrel in vivo. In this study, we aimed to assess therelationship between ABCB1gene polymorphism and CR, by polymerase chainreaction(PCR) and sequencing analysis.Methods:500patients with coronary heart disease were involved who were treated with clopidogrel(600mg or300mg) and aspirin(300mg). Clopidogrelresponse was assessed by posttreatment ADP20μmol/L-induced plateletaggregation. Genomic DNA was extracted from peripheral blood. TagSNPs areselected form Hapmap. Clopidogrel resistance was defined by RPA (RPA≥70%).Genotypes were determined by polymerase chain reaction(PCR) and sequencinganalysis for tag single nucleotide polymorphism (tagSNPs) of ABCB1gene.Results:(1) There are9selected tagSNPs in the study, including rs1922242，rs2235048，rs10808072，rs1989831，rs868755，rs4148733，rs1202184，rs1045642and rs13233308.(2) ABCB1rs1045642(C3435T）polymorphism were CC,CTand TT genotypes, in CR group and NCR group were23.3%、46.0%、30.7%and37.7%、44.3%、18.0%. T allele carriers in CR group are much more than those inNCR group（53.7%vs40.1%，p<0.001）.(3) ABCB1rs1922242，rs2235048，rs10808072，rs1989831，rs868755，rs4148733，rs1202184and rs13233308polymorphism were not significant correlated with CR (P>0.05).Conclusion: ABCB1rs1045642(C3435T）may be an independent risk factor forclopidogrel resistance.