急性冠脉综合征患者细胞色素P450的2C19基因多态性与氯吡格雷抗血小板作用及其预后的关系研究

发布时间：2018-10-19 18:20

【摘要】：背景临床上氯吡格雷的治疗效果普遍存在个体差异,这与患者种族相关并受其基因型影响。目的探讨急性冠脉综合征患者细胞色素P450的2C19(CYP2C19)基因多态性与氯吡格雷抗血小板作用及其预后之间的关系,以期为以基因分型为指导的个体化抗血小板治疗提供依据。方法选取2012年3—12月在航天中心医院心脏中心住院治疗的急性冠脉综合征患者98例为研究对象。入院后给予患者氯吡格雷单次负荷剂量300 mg而后75 mg/d口服,或直接给予75 mg/d常规剂量口服。分别检测患者入院时、治疗3 d后血小板聚集率,血小板抑制率,氯吡格雷抵抗情况。采用Taqman-PCR技术检测患者CYP2C19基因型,根据CYP2C19基因检测结果,按照是否携带突变基因A将患者分为野生型组(第5外显子G681A位点和第4外显子G636A位点均无突变基因A,34例)和突变型组(第5外显子G681A位点或第4外显子G636A位点有突变基因A,64例)。随访患者主要心血管不良事件(MACEs)发生情况。结果 CYP2C19*2基因型和CYP2C19*3基因型均符合Hardy-Weinberg平衡定律(P0.05),提示本研究纳入的样本具有较好的群体代表性。不同CYP2C19*2基因型患者入院时血小板聚集率比较,差异无统计学意义(P0.05)。CYP2C19*2中,GA基因型患者治疗3 d后血小板聚集率大于GG基因型(P0.05);CYP2C19*2中,AA基因型患者治疗3 d后血小板聚集率大于GG、GA基因型(P0.05)。CYP2C19*2中,GA、AA基因型患者血小板抑制率小于GG基因型(P0.05)。CYP2C19*2中,GG、GA基因型患者治疗3 d后血小板聚集率均小于入院时血小板聚集率(P0.05)。不同CYP2C19*3基因型患者入院时血小板聚集率、治疗3 d后血小板聚集率、血小板抑制率比较,差异无统计学意义(P0.05)。CYP2C19*3中,GG、GA基因型患者治疗3 d后血小板聚集率小于入院时血小板聚集率(P0.05)。野生型组患者氯吡格雷抵抗发生率小于突变型组(P0.05)。野生型组MACEs发生率小于突变型组(P0.05)。CYP2C19*2中,GG基因型患者MACEs发生率小于AA基因型(P0.05);CYP2C19*2中,GA基因型患者MACEs发生率小于AA基因型(P0.05)。不同CYP2C19*3基因型患者MACEs发生率比较,差异无统计学意义(P0.05)。结论急性冠脉综合征患者CYP2C19基因多态性与氯吡格雷抗血小板作用相关,含有CYP2C19第5外显子突变者服用常规剂量氯吡格雷后抗血小板作用减弱,预后较差,而第4外显子突变对患者预后影响相对较小。
[Abstract]:Background the clinical efficacy of clopidogrel is different in individuals, which is related to race and affected by genotype of clopidogrel. Objective to investigate the relationship between cytochrome P450 2C19 (CYP2C19) gene polymorphism and antiplatelet effect and prognosis of clopidogrel in patients with acute coronary syndrome (ACS) in order to provide evidence for individualized antiplatelet therapy guided by genotyping. Methods 98 patients with acute coronary syndrome (ACS) who were hospitalized in the heart center of Aerospace Center Hospital from March to December 2012 were selected. After admission, patients were given clopidogrel at a single dose of 300 mg and then orally for 75 mg/d, or directly at a conventional dose of 75 mg/d. The platelet aggregation rate, platelet inhibition rate and clopidogrel resistance were measured 3 days after admission. The CYP2C19 genotypes of patients were detected by Taqman-PCR technique. According to the results of CYP2C19 gene detection, The patients were divided into wild-type group (34 cases at exon 5 G681A locus and exon 4 G636A locus) and mutant group (exon 5 G681A locus or exon 4 G636A locus) according to whether they carried mutant gene A or not. There were 64 cases with mutation gene AN. Major cardiovascular adverse events (MACEs) were followed up. Results both CYP2C19*2 genotypes and CYP2C19*3 genotypes were in accordance with the Hardy-Weinberg equilibrium law (P0.05), which suggested that the samples included in this study had better population representation. Comparison of platelet aggregation rate at admission in patients with different CYP2C19*2 genotypes, In CYP2C19*2, the platelet aggregation rate of patients with GA genotype was higher than that of GG genotype after 3 days treatment (P0.05); in CYP2C19*2 patients with AA genotype was higher than that of GG,GA genotype after 3 days treatment (P0.05). In CYP2C19*2, the platelet aggregation rate of GA,AA genotype patients was higher than that of GG,GA genotype patients (P0.05). In CYP2C19*2, the platelet aggregation rate of GA,AA genotype patients was higher than that of GG,GA genotype patients (P0.05). In CYP2C19*2, the platelet aggregation rate of patients with GG,GA genotype was lower than that of patients with GG,GA genotype 3 days after treatment (P0.05). The platelet aggregation rate at admission, platelet aggregation rate and platelet inhibition rate in patients with different CYP2C19*3 genotypes were compared after 3 days of treatment. There was no significant difference (P0.05). In CYP2C19*3, the platelet aggregation rate of GG,GA genotype patients was lower than that of admission patients 3 days after treatment (P0.05). The incidence of clopidogrel resistance in wild type group was lower than that in mutant group (P0.05). The incidence of MACEs in wild type group was lower than that in mutant group (P0.05). In CYP2C19*2, the incidence of MACEs in GG genotype was lower than that in AA genotype (P0.05); in CYP2C19*2, MACEs incidence rate in GA genotype was lower than that in AA genotype (P0.05). There was no significant difference in the incidence of MACEs among patients with different CYP2C19*3 genotypes (P0.05). Conclusion the polymorphism of CYP2C19 gene in patients with acute coronary syndrome is associated with clopidogrel's antiplatelet effect. The antiplatelet effect of clopidogrel was weakened and the prognosis was poor in patients with CYP2C19 exon 5 mutation. But exon 4 mutation has relatively little effect on prognosis.
【作者单位】：航天中心医院心脏中心;北京大学人民医院心脏中心;河北中医学院中西医结合学院;汕头大学医学院第一附属医院心血管内科;
【分类号】：R543.3

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