急性心肌梗死患者氧磷酶1 Q192R基因多态性与氯吡格雷抵抗的相关性

Association between paraoxonase-1 Q192R gene polymorphism and clopidogrel resistance in patients with acute myocardial infarction

  • 摘要:
    目的 分析急性心肌梗死患者氧磷酶1(PON1)Q192R基因多态性与氯吡格雷抵抗的相关性。
    方法 选取135例急性心肌梗死患者为研究对象,所有患者在院服用标准剂量氯吡格雷,连服5 d, 出院后连续用药12个月,用药12个月后到院测定血小板聚集率。患者按照血小板聚集率分为抵抗组(聚集率>50%)和敏感组(≤50%)。采用荧光原位杂交法检测PON1 Q192R基因多态性。
    结果 135例急性心肌梗死患者经血小板聚集测定,敏感组103例(76.30%), 抵抗组32例(23.70%)。抵抗组患者PON1 Q192R基因分布单核苷酸多态性(SNP)杂合子型、SNP纯合子型发生率高于敏感组,差异有统计学意义(P < 0.05)。抵抗组术后1年终点事件发生率高于敏感组,差异有统计学意义(P < 0.05)。PON1 Q192R基因野生型的二磷酸腺苷(ADP)血小板聚集率、主要心血管不良事件(MACE)发生率低于突变型,差异有统计学意义(P < 0.05)。PON1 Q192R基因突变与ADP血小板聚集率是急性心肌梗死患者MACE发生的危险因素(P < 0.05)。PON1 Q192R基因SNP杂合子型、SNP纯合子型与氯吡格雷抵抗的发生显著相关(P < 0.05)。
    结论 急性心肌梗死患者PON1 Q192R基因多态性与氯吡格雷抵抗相关性较高。

     

    Abstract:
    Objective To analyze the correlation between paraoxonase-1 (PON1) Q192R gene polymorphism and clopidogrel resistance in patients with acute myocardial infarction.
    Methods A total of 135 patients with acute myocardial infarction were selected as research objects. All patients were treated with standard clopidogrel for 5 consecutive days and post-discharge for 12 months continuously. After 12 months of medication, the platelet aggregation rate was measured in the hospital. Patients were divided into resistance group (aggregation rate >50%) and sensitive group (≤50%) according to platelet aggregation rate. PON1 Q192R gene polymorphism was detected by fluorescence in situ hybridization.
    Results Platelet aggregation was determined in 135 patients with acute myocardial infarction, 103 cases (76.30%) in the sensitive group and 32 cases (23.70%) in the resistance group. The incidence rates of heterozygous and homozygous single nucleotide polymorphisms (SNP) of PON1 Q192R gene distribution in the resistance group were significantly higher than those in the sensitive group (P < 0.05). The incidence of end-point events at one year after operation in the resistance group was significantly higher than that in the sensitive group (P < 0.05). The platelet aggregation rate of adenosine diphosphate (ADP) and the incidence of major adverse cardiovascular events (MACE) in PON1 Q192R wild-type were significantly lower than those in PON1 Q192R mutant (P < 0.05). PON1 Q192R gene mutation and ADP platelet aggregation ratewere risk factors for MACE in patients with acute myocardial infarction (P < 0.05). SNP heterozygous type and SNP homozygous type of PON1 Q192R gene were significantly correlated with clopidogrel resistance (P < 0.05).
    Conclusion PON1 Q192R gene polymorphisms has higher correlation with clopidogrel resistance in patients with AMI.

     

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