Department of Pathology, The Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
Am J Clin Pathol. 2013 Feb;139(2):202-7. doi: 10.1309/AJCP9K2KDOCPCBSV.
Conversion of clopidogrel (Plavix) to its active metabolite is catalyzed largely by the P450 enzyme 2C19 (CYP2C19). Numerous allelic variants of CYP2C19 exist. The *1 allele is considered wild type, whereas the *2 and *3 alleles have no in vivo enzymatic activity. Conversely, the *17 allele has increased expression, resulting in increased clopidogrel activation. Poor metabolizers (*2/*2 and *2/*3 genotypes) experience higher rates of therapeutic failure. For this reason, we have validated a CYP2C19 genotyping assay for the *1, *2, *3, and 17 alleles. Genomic DNA extracted from 30 deidentified EDTA whole-blood samples from patients was analyzed at 2 independent facilities using specific TaqMan realtime polymerase chain reaction primers and probes. Concordant genotypes were generated on all samples tested. Of the 30 samples, 15 were CYP2C191/1, 8 were CYP2C191/17, 5 were CYP2C191/2, and 2 were CYP2C192/17. There were no CYP2C193 alleles or *2/*2 homozygous genotypes detected. This CYP2C19 genotyping assay is appropriate for clinical testing, demonstrating excellent interlaboratory concordance, enabling the selection of the most effective clopidogrel treatment regimen for patients undergoing percutaneous coronary intervention.
氯吡格雷（波立维）向其活性代谢物的转化主要由 P450 酶 2C19（CYP2C19）催化。CYP2C19 存在许多等位基因变异。1 等位基因被认为是野生型，而2 和*3 等位基因没有体内酶活性。相反，*17 等位基因表达增加，导致氯吡格雷激活增加。代谢不良者（2/2 和2/3 基因型）经历更高的治疗失败率。出于这个原因，我们已经验证了 CYP2C19 基因分型测定法用于1、2、3 和17 等位基因。使用特定的 TaqMan 实时聚合酶链反应引物和探针，从 30 名来自患者的 EDTA 全血的匿名样本中提取基因组 DNA，并在 2 个独立的设施中进行分析。在所有测试的样本中均生成了一致的基因型。在 30 个样本中，15 个是 CYP2C191/1，8 个是 CYP2C191/17，5 个是 CYP2C191/2，2 个是 CYP2C192/17。未检测到 CYP2C193 等位基因或2/*2 纯合基因型。这种 CYP2C19 基因分型测定法适合临床检测，显示出出色的实验室间一致性，能够为接受经皮冠状动脉介入治疗的患者选择最有效的氯吡格雷治疗方案。
