Influence of <i>CYP2C19</i>
 loss-of-function variants on the metabolism of clopidogrel in patients from north-western China

Lin, Rong; Zhang, L.; Zhang, P.; Zhou, Liming; Liu, Tie; Li, Y.; Zhang, W.; Wang, W.; Zhang, J.

doi:10.1111/jcpt.12254

Cited by 16 publications

(9 citation statements)

References 33 publications

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“…Clopidogrel has no biological activity; it is metabolized into 15% active metabolite and 85% inactive metabolite by the P450 system. The polymorphic isoenzyme CYP2C19 plays an essential role in genetic diversity [ 21 ]. There were 101 patients (28.8%) who suffered MACE during the 1-year follow-up in the current study.…”

Section: Discussionmentioning

confidence: 99%

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study

Wang

Bai

et al. 2021

BMC Cardiovasc Disord

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Background Acute coronary syndrome (ACS) has become a vital disease with high mortality in the Uygur populations. Clopidogrel plays an important role in reducing the risk of recurrent cardiovascular events after ACS; however, it is a prodrug that requires biotransformation by cytochrome P450 (CYP450). Objectives To determine the effect of genetic polymorphisms in CYP2C19*2, *3, and *17, and along with clinical, demographic factors, on variation in response to clinical outcomes in Uygur patients. Methods A total of 351 patients with ACS were treated with clopidogrel and aspirin for at least 12 months; we recorded major adverse cardiovascular events (MACE) or bleeding within 1 year. Multivariable logistic regression analyses were carried out to identify factors associated with MACE or bleeding. Results We analyze risk factors include age, BMI (body mass index), smoking, alcohol intake, NSTEMI (non-ST-segment elevation myocardial infarction), hypertension, dyslipidemia, concomitant medication, CYP2C19*2 carriers, CYP2C19*17 carriers and metabolizer phenotype. CYP2C19*2 carriers had an odds of having MACE of 2.51 (95% CI: 1.534–4.09) compared with noncarriers (P < .001). However, no factors were significantly associated with bleeding (P > 0.05). Conclusion The CYP2C19*2 gene polymorphism contributes to the risk of MACE in dual clopidogrel—treated Uygur population with ACS with or without PCI (percutaneous coronary intervention). These data may provide valuable insights into the genetic polymorphisms affecting clopidogrel metabolism among minority groups in China.

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Section: Discussionmentioning

confidence: 99%

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study

Wang

Bai

et al. 2021

BMC Cardiovasc Disord

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“…The polymorphic isoenzyme CYP2C19 plays an important part in genetic diversity. [ 22 ] Interpersonal differences in metabolic activities may be reflected in drug pharmacokinetics as well as in therapeutic outcomes of CYP2C19 substrates. [ 23 ]…”

Section: Discussionmentioning

confidence: 99%

CYP2C19, PON1, and ABCB1 gene polymorphisms in Han and Uygur populations with coronary artery disease in Northwestern Xinjiang, China, From 2014 Through 2019

Wang¹,

Zhao²,

Bao³

et al. 2020

Medicine

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The morbidity of coronary artery disease (CAD) in the Uygur population of Xinjiang was much higher than the national average. Clopidogrel is the most commonly used medication worldwide in dual antiplatelet therapy for CAD, and the response of clopidogrel is affected by CYP2C19 , PON1 , and ABCB1 genetic polymorphisms. The distribution of CYP2C19∗17 , ABCB1 , and PON1 genetic polymorphisms in Han and Uygur populations with CAD of Xinjiang has not been investigated. This study aimed to investigate the frequencies of CYP2C19 , PON1 , and ABCB1 genetic polymorphisms, and to identify the metabolizer phenotype of CYP2C19 in Han and Uygur populations with CAD in Northwestern Xinjiang, China. We identified 602 Han and 527 Uygur patients from 2014 through 2019 and studied genotypes for selected allele polymorphisms using sequencing by hybridization. There were significantly different allele frequencies and genotype frequencies between the 2 ethnic groups in terms of CYP2C19∗2, ∗3, ∗17 , ABCB1 and PON1 , ( P < .05). For CYP2C19∗17 , the frequency of TT genotype was 2.5% in Uygur patients, but it was undetectable in Han patients. In both the intermediate and poor metabolizer groups, the genotypes polymorphisms CYP2C19∗2, ∗3, ∗17 were significantly less common in Uygur patients than in Han patients ( P < .001). By contrast, the proportion of ultra-metabolizers as defined by CYP2C19∗2, ∗3, ∗17 polymorphisms significantly higher in Uygur patients (18.6%) than in Han patients (1.7%, P < .001). The CYP2C19∗2 frequency was significantly different between Han patients and Han healthy groups ( P < .001), while the CYP2C19∗3 frequency was significantly different between Uygur patients and Uygur healthy groups ( P < .001). Our study supports the notion of interethnic differences in terms of CYP2C19 , PON1 , and ABCB1 polymorphisms and CYP2C19 genotype-defined clopidogrel metabolic groups. These finding could provide valuable data and insights into personalized CAD treatment for the Uygur and Han populations in Xinjiang.

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“…For clopidogrel-resistant patients, CYP2C19 mutation detection can aid clinicians to switch patients to more effective antiplatelet therapy such as prasugrel or ticagrelor, to overcome their poor response to clopidogrel. 22,23 Indeed, PCI postoperative clopidogrel antiplatelet therapy is one of the most effective ways to reduce the risk of thrombosis. 21,24…”

Section: Discussionmentioning

confidence: 99%

Clinical application and importance of one-step human CYP2C19 genotype detection

et al. 2018

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BackgroundTo directly achieve cytochrome P450 2C19 gene (CYP2C19) classification using one-step real-time fluorescent PCR detection and to verify the capabilities of this method with nucleic acid extracted from whole blood samples.MethodsA human CYP2C19 genotyping kit based on one-step real-time fluorescent PCR detection was used to analyze whole blood or genomic DNA samples. This method was compared with pyrosequencing and another quantitative (q)PCR kit for its accuracy, repeatability, detection range analysis, sensitivity, specificity, and anti-interference analysis.ResultsThe one-step real-time PCR method achieved a 100% accuracy rate compared with pyrosequencing and the other qPCR kit. When detecting different concentrations of known genes, concentrations of each sample ranging from 0.2 to 125 ng/µL could be correctly detected. The genotypes of samples treated with anticoagulants, including EDTA and sodium citrate, and chyle blood samples could be correctly detected.ConclusionThe one-step detection method demonstrated high accuracy and a wide detection range. It also had high levels of repeatability, sensitivity, and specificity for the assessment of genomic DNA test samples.

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Influence of CYP2C19 loss-of-function variants on the metabolism of clopidogrel in patients from north-western China

Cited by 16 publications

References 33 publications

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study

Association between cytochrome P450 2C19 polymorphism and clinical outcomes in clopidogrel-treated Uygur population with acute coronary syndrome: a retrospective study

CYP2C19, PON1, and ABCB1 gene polymorphisms in Han and Uygur populations with coronary artery disease in Northwestern Xinjiang, China, From 2014 Through 2019

Clinical application and importance of one-step human CYP2C19 genotype detection

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