Influence of CYP2C19, ABCB1 and PON1 genotypes on the plasma concentrations of clopidogrel metabolite and platelet aggregation in patients after coronary stenting (PCI)

Gawrońska-Szklarz, B; Czerkawska, Anna; Adamiak-Giera, Urszula; Olędzki, Szymon; Kurzawski, Mateusz; Jastrzębska, Maria; Safranow, Krzysztof; Kornacewicz-Jach, Zdzisława

doi:10.1016/s1734-1140(13)71326-4

Cited by 2 publications

(2 citation statements)

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“…Clopidogrel is a precursor drug that is converted into its active form through 2 sequential oxidative steps after absorption into the bloodstream via the intestines [17]. Studies have shown that the enzymes encoded by the ABCB1 , CY2C19 , and PON1 genes influence clopidogrel metabolism by affecting the absorption and activation of clopidogrel [18]. Thus far, the majority of studies that investigated the associations between ABCB1 , CY2C19 and PON1 polymorphisms and CR have been conducted in western populations [19].…”

Section: Introductionmentioning

confidence: 99%

Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China

Yang

et al. 2019

Med Sci Monit

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BackgroundThe relationship between clopidogrel-resistance (CR) and polymorphism located in genes encoding clopidogrel metabolism-related enzymes has not been fully explored. Thus far, few studies on CR-associated polymorphism have been conducted in the Chinese population. The purpose of this study was to identify CYP2C19 polymorphism associated with CR in patients with acute coronary syndrome in China.Material/MethodsThere were 125 patients with acute coronary syndromes (ACS) selected for this study. Of these, 27 patients (21.6%) showed CR (less than 10% reduction in platelet accumulation rate), while the remaining 98 patients (78.4%) were non-clopidogrel-resistant (NCR).ResultsThere were significant differences in the allele frequencies of CYP2C19 (rs4244285) (P=0.03) and CYP2C19 (rs4986893) (P=0.005) between the 2 groups; however, there was no significant difference in allele frequencies of ABCB1 (rs1045642) (P=0.661) and PON1 (rs662) (P=0.690) between the 2 groups. The null allele in the CYP2C19 (rs4244285) [odds ratio (OR)=5.317, 95% confidence interval (CI) 1.542–26.428, P=0.001] and CYP2C19 (rs4986893) (OR=4.295, 95%CI 1.312–17.517, P=0.013) is one of the causes of CR in patients with ACS in China.ConclusionsThe CYP2C19 polymorphism (rs4244285 and rs4986893) is the correlative factor of CR in patients with ACS in China. It was found that the null allele in the CYP2C19 polymorphism was related to the higher CR risk. According to the key role of CYP2C19 in the clopidogrel activation and the evaluated role of CYP2C19 in this study, further studies should be carried out to formulate therapeutic alternative methods for CR in patients with ACS.

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Section: Introductionmentioning

confidence: 99%

Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China

Yang

et al. 2019

Med Sci Monit

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“…As it is known that L54M (rs854560) and Q192R (rs662) polymorphisms have the greatest clinical significance among all the polymorphic variants of the PON1 gene [6], [7], [8], [9]. The CYP2C19 gene has nine exons and it is highly polymorphic with more than 25 allele variants [5].…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms Association in Restenosis of Coronary Arteries

Taizhanova

Bodaubay

Toleuova

et al. 2020

Open Access Maced J Med Sci

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BACKGROUND: There is a reason to believe that the polymorphism of genes encoding some enzymes and receptors plays a role in increasing of restenosis development risk. It is common knowledge that ethnicity affects the frequency of heterozygous genotypes occurrence. There is the evidence that polymorphism of the FGB gene (rs1800790) and THBD gene was determined in the ethnic group of Kazakhs with restenosis of the coronary arteries, which can be considered as genetic predictors of restenosis development. Today, the questions of the role of the genetic component in the development of coronary heart disease (CHD) remain open. AIM: Evaluation of gene polymorphism in patients with restenosis of coronary arteries after stent installation. MATERIALS AND METHODS: The group consisted of Kazakh population of the age category from 45 to 65 years of both sexes: Group I (50 persons) patients with a diagnosis of CHD, with a fixed stent and the development of restenosis during the year; Group 2 (58 persons) – with a fixed stent and no restenosis during the year. The association of genetic polymorphisms was evaluated in accordance with the case–control design based on the generalized linear model assuming a log-additive inheritance model. RESULTS: Thus, when comparing two groups using five patterns of inheritance, the following SNP were revealed: Codominant inheritance pattern – rs1045642 (p = 0.0427), dominant inheritance pattern – rs12041331 (p = 0.036088), rs13431554 (p = 0.025461), and rs1045642 (p = 0.012774), and overdominant inheritance pattern – rs12041331 (p = 0.051736), rs5918 (p = 0.057652), and rs13431554 (р = 0.036006). Thus, three SNPs associated with stenting were identified: rs7543130 (p = 0.009324), rs6785930 (p = 0.016858), and rs7819412 (p = 0.061325) and two SNPs associated with the development of restenosis after stent placement: rs1061781 (p = 0.063184) and rs342293 (p = 0.061636). CONCLUSION: The polymorphisms associated with the risk of developing restenosis after stenting were determined: Codominant inheritance pattern – one polymorphism (rs1045642, p = 0.0427); dominant inheritance pattern – three polymorphisms (rs12041331, p = 0.036088; rs13431554, p = 0.025461; rs1045642, p = 0.012774), and overdominant inheritance pattern – one polymorphism (rs13431554, p = 0.036006). Based on the hybrid machine learning approach (RuleFit), four rules were obtained for assessing the empirical risk of restenosis developing after stenting – from 20% to 40%.

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Influence of CYP2C19, ABCB1 and PON1 genotypes on the plasma concentrations of clopidogrel metabolite and platelet aggregation in patients after coronary stenting (PCI)

Cited by 2 publications

References 0 publications

Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China

Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China

Genetic Polymorphisms Association in Restenosis of Coronary Arteries

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