CAJ | 학술논문

目的:探讨细胞色素P450(cytochrome,CYP)2C19*17等位基因变异对中国冠心病血瘀证患者经皮冠状动脉介入术(percutaneous coronary intervention,PCI)后应用氯吡格雷治疗的血小板聚集率及出血事件的影响.方法:以限制性片段长度多态性聚合酶链反应基因分析方法检测C YP2C 19*17基因多态性,研究2009年7月至2011年4月福建省立医院心内科择期进行PCI成功的冠心病血瘀证患者520例.PCI术前常规服用阿司匹林300 mg、氯吡格雷300 mg.术前采血,制备富血小板血浆、贫血小板血浆及二磷酸腺苷(adenosine diphosphate,ADP)诱导剂,采用比浊法,以最终浓度为5 μmol/L ADP为诱导剂,在氯吡格雷治疗前及治疗后10d,检测血小板聚集率.分析最大血小板聚集率(maximal aggregation,Aggmax)和残余血小板聚集率(5-min aggregation,Agglate).结果:试验发现有5.96％的患者发生心肌梗死血栓溶解术出血事件,而本试验中病人的CYP2C19*17等位基因频率为7.98％.对于CYP2C19 *17等位基因携带者,其出血事件发生率远高于野生型(P＜0.01)；在基线水平,5 μ mol/L ADP诱导的Aggmax和Agglate以及血小板聚集率在CYP2C19*17各基因型之间并没有显著区别；然而经氯吡格雷治疗10 d后,CYP2C19 *17等位基因携带者与野生型相比,上述3项指标均明显降低(P＜0.01或P＜0.05),血小板聚集抑制率显著高于野生型患者(P＜0.01)；携带有CYP2C19* 17等位基因的患者与野生型相比,具有更高的出血风险(P＜0.01).结论:冠心病血瘀证患者CYP2C19*17等位基因携带者有着显著的氯吡格雷反应性且其出血风险明显增加.
목적:탐토세포색소P450(cytochrome,CYP)2C19*17등위기인변이대중국관심병혈어증환자경피관상동맥개입술(percutaneous coronary intervention,PCI)후응용록필격뢰치료적혈소판취집솔급출혈사건적영향.방법:이한제성편단장도다태성취합매련반응기인분석방법검측C YP2C 19*17기인다태성,연구2009년7월지2011년4월복건성립의원심내과택기진행PCI성공적관심병혈어증환자520례.PCI술전상규복용아사필림300 mg、록필격뢰300 mg.술전채혈,제비부혈소판혈장、빈혈소판혈장급이린산선감(adenosine diphosphate,ADP)유도제,채용비탁법,이최종농도위5 μmol/L ADP위유도제,재록필격뢰치료전급치료후10d,검측혈소판취집솔.분석최대혈소판취집솔(maximal aggregation,Aggmax)화잔여혈소판취집솔(5-min aggregation,Agglate).결과:시험발현유5.96％적환자발생심기경사혈전용해술출혈사건,이본시험중병인적CYP2C19*17등위기인빈솔위7.98％.대우CYP2C19 *17등위기인휴대자,기출혈사건발생솔원고우야생형(P＜0.01)；재기선수평,5 μ mol/L ADP유도적Aggmax화Agglate이급혈소판취집솔재CYP2C19*17각기인형지간병몰유현저구별；연이경록필격뢰치료10 d후,CYP2C19 *17등위기인휴대자여야생형상비,상술3항지표균명현강저(P＜0.01혹P＜0.05),혈소판취집억제솔현저고우야생형환자(P＜0.01)；휴대유CYP2C19* 17등위기인적환자여야생형상비,구유경고적출혈풍험(P＜0.01).결론:관심병혈어증환자CYP2C19*17등위기인휴대자유착현저적록필격뢰반응성차기출혈풍험명현증가.
OBJECTIVE:To assess the impact of cytochrome P450 (CYP) 2C19*17 allelic variant on platelet aggregation and bleeding risk in Chinese patients with blood stasis syndrome undergoing percutaneous coronary intervention (PCI) and treated with clopidogrel.METHODS:A total of 520 patients with blood stasis syndrome undergoing PCI after pretreatment with 300 mg clopidogrel and aspirin were studied from July 2009 to April 2011 in Fujian Provincial Institute of Cardiovascular Diseases.CYP2C19*17 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism.Platelet aggregation induced by 5 μmol/L of adenosine diphosphate (ADP) was analyzed with platelet-rich plasma and platelet-poor plasma by turbidimetry method before and after 10 d of treatment with clopidogrel.RESULTS:Bleeding events were observed in 5.96％ of patients after thrombolysis for myocardial infarction,and the ratio of patients with CYP2C19*17 allele was 7.98％.The bleeding rate in patients carrying CYP2C19* 17 allele,heterozygous (wt/* 17) and homozygous (* 17/* 17),was higher than that in patients with wild-type homozygotes (wt/wt) (P＜0.01).At baseline,ADP-induced light transmission at maximal aggregation,5-min aggregation and disaggregation showed no significant difference among patients with the three different CYP2C19* 17 genotypes.However,after 10-day administration of clopidogrel,values of ADP-induced platelet aggregation in *17/* 17 and wt/* 17 carriers were significantly decreased compared with the wild-type homozygotes (P＜0.05,P＜0.01) ; the inhibition rate of platelet aggregation was higher in patients carrying *17/*17 and wt/* 17 than those only carrying wt/wt,and the same result was found in disaggregation of platelet after 10-day treatment (P＜0.05,P＜0.01).Patients with wt/*17 and *17/*17 allele of CYP2C19 showed a higher risk of bleeding than those with wildtype allele (P＜0.01),and the occurrence of bleeding was highest in patients with CYP2C19*17homozygotes.CONCLUSION:CYP2C19*1 7 allele is associated with enhanced response to clopidogrel and an increased risk of bleeding in patients with blood stasis syndrome of coronary artery disease treated by clopidogrel.