The Relationship Between CYP450s, ABCB1Genotypes And The Recurrence Risk Of Stroke In Patients Received Clopidogrel Therapy With Acute Ischemic Stroke In China

Purpose To investigate the distribution of genetic polymorphisms ofCYP2C19*2,*3,*17,CYP2C9*3and ABCB1C3435T inFujian Han population,and analysisthe relationship between those polymorphisms and the recurrence of ischemic stroke in whowere taking clopidogrel threapy.Methods In order to analysis the distribution,Polymerase chain reaction-Restriction fragmentlength polymorphism(PCR-RFLP) and Direct sequencing method were used to detect thegenotypes of CYP2C19*2,*3,*17,CYP2C9*3and ABCB1C3435T.We collected985ischemicstroke patients who inhospital in the first affiliated hospital of Fujian medical university inMarch2011to March2013retrospectively.All were received1year follow-upevaluations,only114patients taking clopidogrel Conventional treatment dose over a year.Weanalysis the correlation between those genotypes and the recurrence of stroke.Furthermore,themodified Rankin Scale (mRS) were used to assess the functional recovery.Results In1000healthy volunteers,the genotype frequencies ofCYP2C19*2,*3,*17,CYP2C9*3and ABCB1C3435T were33.0%,5.75%,0.30%,1.95%and41.85%respectively.CYP2C19gene polymorphism, intermediate metabolizers andintermediate metabolizers accounted for47.7%and14.9%.However,According to theABCB1C3435T gene polymorphism, high metabolic type (CC), intermediate type (CT) andlow metabolic type (TT) accounted for32.0%,52.3%and32.0%respectively.In those takingclopidogrel for1year(n=114),23suffered from Secondary attack. Compared with extensivemetabolizer, the CYP2C19poor metabolizer was related to higher risk of cerebrovascularevents (OR=2.156, P=2.156). patients carrying CYP2C19loss-of-function alleles (*2)were more likely to suffered a relapse than those carrying none (OR=2.993, P=2.993).Ahistory of stroke was proved to be a risk factors.However,CYP2C19*3、*17、CYP2C9*3and ABCB1C3435T polymorphisms did not associated with the recurrence rate of stroke.Conclusions There are racial differences inthe distribution of CYP2C19, CYP2C9polymorphisms,while no difference was found between our research and North hanpopulation,south han Chinese,east Asia and the Japanese.In the follow up, we found thatCYP2C19*2gene polymorphism was an independent risk factor for the recurrence ofcerebral apoplexy.Furthermore, a history of stroke is more prone to recurrence ofstroke.CYP2C19*3, CYP2C19*17, CYP2C9*3and ABCB1genetic polymorphismsshowed no relationship with the recurrence.