CAJ | 학술논문

目的：分析汉族急性缺血性脑卒中患者CYP2C19基因多态性与氯吡格雷抵抗的关系。方法2012年7月—2014年9月连续性纳入住院并服用氯吡格雷抗血小板聚集治疗（75 mg／d，连续＞7 d）的急性缺血性脑卒中患者72例。根据对二磷酸腺苷（ADP）诱导的血小板聚集抑制率将患者分为氯吡格雷抵抗（CR）组（27例）和非抵抗（NCR）组（45例）。基因芯片法检测受试者的CYP2C19基因型，依据突变类型，分为快代谢型（倡1／倡1）、中间代谢型（倡1／倡2、倡1／倡3）和慢代谢型（倡2／倡2、倡2／倡3、倡3／倡3）。采用多元Logistic回归分析筛选与发生氯吡格雷抵抗相关的危险因素。结果2组 CYP2C19基因型的分布比较差异有统计学意义（χ2＝32?．302， P ＜0．05）；检出CYP2C19基因型为慢代谢型7例（9．7％），中间代谢基因型39例（54．2％），快代谢型26例（36．1％）；3组的血小板聚集抑制率分别为（67．5±21．6）％、（57．6±23．4）％和（31．4±15．1）％，慢代谢型＞中间代谢型＞快代谢型（ P ＜0．01）。多因素Logistic回归分析结果显示 CYP2C19慢代谢型（倡2／倡2、倡2／倡3）（ OR ＝7．802，95％CI 1．412～40．304， P ＝0．018）和低密度脂蛋白水平＞2．6 mmol／L（OR＝3．923，95％CI 1．314～17．927， P ＝0．032）是发生氯吡格雷抵抗的独立危险因素。结论汉族急性缺血性脑卒中患者中，CYP2C19慢代谢基因型（倡2／倡2、倡2／倡3）和低密度脂蛋白水平升高是导致氯吡格雷抵抗的独立危险因素。
목적：분석한족급성결혈성뇌졸중환자CYP2C19기인다태성여록필격뢰저항적관계。방법2012년7월—2014년9월련속성납입주원병복용록필격뢰항혈소판취집치료（75 mg／d，련속＞7 d）적급성결혈성뇌졸중환자72례。근거대이린산선감（ADP）유도적혈소판취집억제솔장환자분위록필격뢰저항（CR）조（27례）화비저항（NCR）조（45례）。기인심편법검측수시자적CYP2C19기인형，의거돌변류형，분위쾌대사형（창1／창1）、중간대사형（창1／창2、창1／창3）화만대사형（창2／창2、창2／창3、창3／창3）。채용다원Logistic회귀분석사선여발생록필격뢰저항상관적위험인소。결과2조 CYP2C19기인형적분포비교차이유통계학의의（χ2＝32?．302， P ＜0．05）；검출CYP2C19기인형위만대사형7례（9．7％），중간대사기인형39례（54．2％），쾌대사형26례（36．1％）；3조적혈소판취집억제솔분별위（67．5±21．6）％、（57．6±23．4）％화（31．4±15．1）％，만대사형＞중간대사형＞쾌대사형（ P ＜0．01）。다인소Logistic회귀분석결과현시 CYP2C19만대사형（창2／창2、창2／창3）（ OR ＝7．802，95％CI 1．412～40．304， P ＝0．018）화저밀도지단백수평＞2．6 mmol／L（OR＝3．923，95％CI 1．314～17．927， P ＝0．032）시발생록필격뢰저항적독립위험인소。결론한족급성결혈성뇌졸중환자중，CYP2C19만대사기인형（창2／창2、창2／창3）화저밀도지단백수평승고시도치록필격뢰저항적독립위험인소。
Objective To analyze the relationship between CYP 2C19 gene polymorphism and clopidogrel resistance in acute ischemic stroke patients .Methods From July 2012 to September 2014 , 72 consecutive patients with acute ischemic stroke (75 mg/d, continuous >7 d) who were hospitalized and treated with clopidogrel .According to the inhibition rate of platelet aggregation induced by ADP , they were divided into clopidogrel resistance (CR) group (27 cases) and non-resistant (NCR) group (45 cases).Gene chip method was used to detect the CYP 2C19 genotype of the subjects .According to the type of mutations, the gene chip was divided into fast metabolic type (*1/*1), intermediate metabolism (*1/*2,*1/*3) and slow metabolism (*2/*2,*2/*3,*3/*3).The risk factors associated with the occurrence of clopidogrel resistance were analyzed by multiple Logistic regression analysis .Results The CYP2C19 genotype distribution were statistically signifi-cant different between the two groups (χ2 =32.302, P <0.05);detected CYP2C19 genotypes were slow metabolism in 7 ca-ses (9.7%), intermediate metabolic genotype 39 cases (54.2%), fast metabolism type in 26 cases (36.1%), 3 groups of platelet aggregation inhibition rate respectively were (67.5 ±21.6)%, (57.6 ±23.4)%and (31.4 ±15.1)%, slow metab-olism type >intermediate metabolizers >metabotropic ( P <0.01).Multivariate logistic regression analysis showed that CYP2C19 slow metabolizers (*2 /*2,*2/*3) (OR=7.802, 95%CI 1.412 to 40.304, P =0.018) and low density lipid protein levels >2.6 mmol /L (OR=3.923, 95%CI 1.314 to 17.927, P =0.032) was independent risk factors for clopidogrel resistance .Conclusion In patients with acute ischemic stroke , CYP2C19 (*2/*2,*2/*3) and low density lipoprotein levels were the independent risk factors for clopidogrel resistance .