Mo Yijun, Lu Yao, Guo Fei, Wu Aihua, Weng Yuesong
Department of Laboratory Medicine, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang, China.
Front Cardiovasc Med. 2023 Feb 2;10:1020593. doi: 10.3389/fcvm.2023.1020593. eCollection 2023.
Certain genetic and non-genetic factors may cause damaged platelet inhibition by clopidogrel. We aimed to determine the effect of () polymorphism, along with other clinical factors, on the platelet response to clopidogrel in patients with acute ischemic stroke (AIS).
A total of 214 patients with AIS receiving clopidogrel at a maintenance dose of 75 mg daily admitted to the Ningbo First Hospital between 1 January 2020, and 31 December 2021, were enrolled. Platelet aggregation analysis was performed to determine clopidogrel resistance. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to determine genotype. Other laboratory data on complete blood count and biochemical parameters were taken from patient medical files.
Among the 214 AIS patients treated with clopidogrel in the Ningbo population, the incidence of clopidogrel resistance was approximately 43.9%, and the distribution of genotypes was highest for (43.0%), followed by (38.8%). The distribution of alleles , , , and was 62.1, 32.5, 4.9, and 0.5%, respectively. A chi-squared test showed that the gene frequencies of alleles and were significantly higher in the clopidogrel-resistant group than in the clopidogrel-sensitive group ( < 0.001), and a Mann-Whitney U-test showed that high HCY levels were significantly correlated with clopidogrel resistance ( < 0.001). Multi-factor logistic regression analysis demonstrated that mutant heterozygous genotype [OR 2.893; 95% confidence interval (CI) 1.456-5.748; = 0.002], mutant homozygous genotype (OR 4.741; 95% CI 1.828-12.298; = 0.001), and high HCY levels (OR 1.209; 95% CI 1.072-1.362; = 0.002) were significantly associated with clopidogrel resistance.
According to our results, carrying the * allele and high HCY levels are independent risk factors for clopidogrel resistance after clopidogrel therapy in patients with AIS. These two factors should be considered prior to clopidogrel administration.
某些遗传和非遗传因素可能导致氯吡格雷对血小板的抑制作用受损。我们旨在确定（）基因多态性以及其他临床因素对急性缺血性卒中（AIS）患者氯吡格雷血小板反应的影响。
纳入2020年1月1日至2021年12月31日期间在宁波市第一医院住院、接受每日75mg维持剂量氯吡格雷治疗的214例AIS患者。进行血小板聚集分析以确定氯吡格雷抵抗情况。采用定量实时聚合酶链反应（QRT-PCR）确定（）基因型。全血细胞计数和生化参数的其他实验室数据取自患者病历。
在宁波人群中接受氯吡格雷治疗的214例AIS患者中，氯吡格雷抵抗的发生率约为43.9%，（）基因型的分布以（）最高（43.0%），其次是（）（38.8%）。等位基因（）、（）、（）和（）的分布分别为62.1%、32.5%、4.9%和0.5%。卡方检验显示，氯吡格雷抵抗组中等位基因（）和（）的基因频率显著高于氯吡格雷敏感组（<0.001），曼-惠特尼U检验显示高同型半胱氨酸（HCY）水平与氯吡格雷抵抗显著相关（<0.001）。多因素逻辑回归分析表明，突变杂合基因型[比值比（OR）2.893；95%置信区间（CI）1.456 - 5.748；=0.002]、突变纯合基因型（OR 4.741；95%CI 1.828 - 12.298；=0.001）和高HCY水平（OR 1.209；95%CI 1.072 - 1.362；=0.002）与氯吡格雷抵抗显著相关。
根据我们的结果，携带（）等位基因和高HCY水平是AIS患者氯吡格雷治疗后氯吡格雷抵抗的独立危险因素。在给予氯吡格雷之前应考虑这两个因素。
