The distribution of CYP2C19 gene polymorphism in patients with acute myocardial infarction and the effect of clopidogrel therapy on adverse cardiovascular events and restenosis after PCI
-
摘要: 目的:检测急性心肌梗死患者CYP2C19基因多态性分布情况,并分析氯吡格雷治疗对PCI术后不良心血管事件和再狭窄的影响。方法:选取我院2018-01—2019-06期间收治的214例行PCI术的急性心梗患者作为研究对象。所有患者PCI术后均给予阿司匹林和氯吡格雷治疗,采用PCR测定患者全血CYP2C19基因分布,比较患者CYP2C19基因型特征,分析其与发生心血管不良事件及再狭窄的关系。结果:214例患者CYP2C19*1、*2、*3等位基因分布频率分别为66.36%、29.21%及4.43%;快代谢型的频率为44.86%,中代谢型的频率为42.99%,慢代谢型的频率为12.15%。其中,发生心血管不良事件组患者快代谢基因型出现的频率为9.76%,中代谢型基因出现的频率为53.65%,慢代谢基因型出现频率为36.59%(P<0.05);且发生心血管不良事件*1等位基因出现频率为36.59%,显著低于未发生组(P<0.05),而*2等位基因及*3等位基因出现频率分别为51.22%及12.19%,均显著高于未发生组,差异有统计学意义(P<0.05)。单因素分析发现患者再狭窄与氯吡格雷抵抗有关(P<0.05)。结论:急性心梗患者PCI术后发生心血管不良事件患者CYP2C19基因突变率较高,主要以中代谢及慢代谢基因型为主,且患者CYP2C19*2和CYP2C19*3基因突变是导致预后发生不良心血管事件及再狭窄的重要原因。Abstract: Objective: To detect the distribution of CYP2 C19 gene polymorphism in patients with acute myocardial infarction and analyze the effect of clopidogrel treatment on adverse cardiovascular events and restenosis after PCI. Method: A total of 214 patients with acute myocardial infarction underwent PCI in our hospital were selected as the study subjects from January 2018 to June 2019. All patients were treated with aspirin and clopidogrel after PCI. PCR was used to determine the distribution of CYP2 C19 gene in the whole blood of the patients. The genotype characteristics of CYP2 C19 of patients were compared, and the relationship between the CYP2 C19 gene and the occurrence of cardiovascular adverse events and restenosis was also analyzed. Result: The distribution frequencies of CYP2 C19*1, *2 and *3 alleles were 66.36%, 29.21% and 4.43%, respectively. The frequency of fast metabolic type was 44.86%, the medium metabolic type was 42.99%, and the slow metabolic type was 12.15%. The frequency of fast metabolic genotypes, medium metabolic genotypes and slow metabolic genotypes in patients with cardiovascular adverse events were 9.76%, 53.65% and 36.59%(P<0.05). Moreover, the occurrence frequency of allele *1 of cardiovascular adverse events was 36.59%, significantly lower than that of allele *1 of the non-occurrence group(P<0.05), and the occurrence frequency of allele *2 and *3 of cardiovascular adverse events were 51.22% and 12.19%, respectively, which significantly higher than that of the non-occurrence group(P<0.05). Single factor analysis found that the restenosis was associated with the clopidogrel resistance(P<0.05).Conclusion: The mutation rate of CYP2 C19 gene in patients with acute myocardial infarction who had cardiovascular adverse events after PCI was high, which the main genotypes were the the middle and slow metabolic genotypes. Meanwhile, the mutation of CYP2 C19*2 and CYP2 C19*3 genes was the important cause of adverse cardiovascular events and restenosis in patients with acute myocardial infarction.
-
-
[1] Cassese S,Byrne RA,Tada T,et al.Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography[J].Heart,2014,100(2):153-159.
[2] 杨利萍,谢婧,刘媱,等.CYP2C19*2、*3基因多态性与氯吡格雷临床疗效相关性的系统评价[J].中国循证医学杂志,2012,12(9):1063-1070.
[3] Aggarwal M,Aggarwal B,RAo J,et al.Integrative medicine for cardiovascular disease and prevention[J].Med Clin North Am,2017,101(5):895-923.
[4] 王涛,李承宗,王来成,等.冠脉介入术患者CYP2C19基因多态性与氯吡格雷应用后心血管事件的相关性研究[J].药学与临床研究,2018,26(4):265-268.
[5] 王慧娟,吴金虎,陈永刚,等.CYP2C19基因多态性分布及不同治疗方案对心血管不良事件的影响[J].中国医院药学杂志,2019,39(19):1946-1949.
[6] 刘丽媚,李雪锋,李存仁,等.冠状动脉支架内再狭窄患者的氯吡格雷抵抗及CYP2C19基因多态性分析[J].中国医药导报,2016,13(21):50-53.
[7] Bliden KP,Di Chiara J,Tantry US,et al.Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention:is the current antiplatelet therapy adequate?[J].J Am Coll Cardiol,2007,49(6):657-666.
[8] 苏强,杨思芸,唐志立,等.川东北CYP2C19基因多态性与氯吡格雷治疗后再发心血管事件相关性研究[J].四川医学,2016,37(5):494-497.
[9] Zhong Z,Hou J,Li B,et al.Analysis of CYP2C19 genetic polymorphism in a large ethnic hakka population in southern China[J].Med Sci Monit,2017,23:6186-6192.
[10] 张昌琳,朱宁.细胞色素P450 2C19多态性与对氯吡格雷的反应性研究进展[J].心血管病学进展,2011,32(6):858-862.
[11] Hwang SJ,Jeong YH,Kim IS,et al.The cytochrome 2C19*2 and *3 alleles attenuate response to clopidogrel similarlyin East Asian patients undergoing elective percutaneous coronary intervention[J].Thromb Res,2011,127(1):23-28.
[12] 梁茜,杨希立,张健瑜,等.CYP2C19基因多态性与氯吡格雷治疗后心血管事件发生关系的研究[J].实用医学杂志,2013,29(23):3883-3884.
[13] 乔斌,汪明,陈振,等.湖北地区心血管疾病患者CYP2C19基因多态性分布情况及临床意义[J].职业与健康,2018,34(14):1939-1941.
[14] Simon T,Verstuyft C,Mary-Krause M,et al.Genetic determinants of response to clopidogrel and cardiovascularevents[J].N Engl J Med,2009,360(4):363-375.
[15] 刘雯,苗佳.CYP2C19基因多态性与个体化治疗的研究进展[J].华西医学,2014,29(12):2382-6.
-
计量
- 文章访问数: 253
- PDF下载数: 265
- 施引文献: 0
下载: