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CYP2C19 *2等位基因频率对巴勒斯坦经皮冠状动脉介入治疗后接受氯吡格雷治疗患者的临床影响。

The clinical effects of CYP2C19 *2 allele frequency on Palestinian patients receiving clopidogrel after percutaneous coronary intervention.

作者信息

Ayesh Basim M, Al-Astal Ibrahim R, Yassin Maged M

机构信息

Department of Laboratory Medical Sciences, Faculty of Medical Sciences, Alaqsa University, Gaza, Palestine.

Naser Medical Complex, Laboratory Department, Ministry of Health, Gaza, Palestine.

出版信息

Int J Clin Pharm. 2019 Feb;41(1):96-103. doi: 10.1007/s11096-018-00782-3. Epub 2019 Jan 17.

Abstract

BackgroundCYP2C19 loss-of-function polymorphic alleles (*2 and *3) have been documented to impair clopidogrel metabolism, and represent a risk factor for major adverse cardiac events. CYP2C19 polymorphism exhibits marked ethnic heterogeneity. Objective To determine the prevalence of CYP2C19 *2 and *3 alleles in a cohort of Palestinian patients managed with percutaneous coronary intervention and dual antiplatelet therapy, and to determine their role in causing major adverse cardiac events. Setting The blood samples were collected at the European Gaza Hospital, and the molecular techniques performed at the molecular genetics laboratory of the Islamic university of Gaza. Method The frequency of CYP2C19 *2 and *3 alleles was determined in 110 patients managed with percutaneous coronary intervention and clopidogrel. Genotyping was performed by PCR-RFLP. Personal and clinical data was obtained from patient record and 6-month follow-up for major adverse cardiac events. Main outcome measureCYP2C19 genotype, personal and clinical data and incidence of major adverse cardiac events. Results The frequency of CYP2C19 *1, *2 and *3 alleles was 82.3%, 15.5% and 2.3% respectively. Genotyping analysis showed that, 67.3% were homozygotes for CYP2C19 *1, 27.3% were *1/*2, 2.7% with *1/*3 genotype, 1.8% were *2/*3 and 0.9% were *2/*2. These frequencies were consistent with those of Caucasian populations. According to this study the poor metabolizers phenotype frequency was 2.7%, which is in the same range reported in Caucasians (2-5%) and lower than Oriental populations 13-23%. A strong significant relation was found between major adverse cardiac events and carrying the variant allele CYP2C19 *2 (P = 0.001). On the other hand, there was no significant relation between major adverse cardiac events and carrying the variant allele CYP2C19 *3 (P = 0.324). Conclusion The CYP2C19 *2 allele is relatively common in our population, and its associated reduced metabolic activity deserves attention as it leads to an increased incidence of major adverse cardiac events in the follow-up of patients receiving clopidogrel.

摘要

背景

已有文献证明,细胞色素P450 2C19(CYP2C19)功能缺失多态性等位基因(2和3)会损害氯吡格雷的代谢,并代表主要不良心脏事件的一个风险因素。CYP2C19多态性表现出显著的种族异质性。目的:确定接受经皮冠状动脉介入治疗和双重抗血小板治疗的巴勒斯坦患者队列中CYP2C19 2和3等位基因的患病率,并确定它们在导致主要不良心脏事件中的作用。背景:血液样本在欧洲加沙医院采集,分子技术在加沙伊斯兰大学分子遗传学实验室进行。方法:在110例接受经皮冠状动脉介入治疗和氯吡格雷治疗的患者中确定CYP2C19 2和3等位基因的频率。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)进行基因分型。从患者记录中获取个人和临床数据,并对主要不良心脏事件进行6个月的随访。主要观察指标:CYP2C19基因型、个人和临床数据以及主要不良心脏事件的发生率。结果:CYP2C19 *1、2和3等位基因的频率分别为82.3%、15.5%和2.3%。基因分型分析显示,67.3%为CYP2C19 1纯合子,27.3%为1/2,2.7%为1/3基因型,1.8%为2/3,0.9%为2/*2。这些频率与白种人群一致。根据本研究,代谢不良者表型频率为2.7%,与白种人报道的范围相同(2%-5%),低于东方人群的13%-23%。发现主要不良心脏事件与携带变异等位基因CYP2C19 *2之间存在强显著相关性(P = 0.001)。另一方面,主要不良心脏事件与携带变异等位基因CYP2C19 *3之间无显著相关性(P = 0.324)。结论:CYP2C19 *2等位基因在我们的人群中相对常见,其相关的代谢活性降低值得关注,因为它会导致接受氯吡格雷治疗的患者在随访中主要不良心脏事件的发生率增加。

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