C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention

Calderón-Cruz, Beatriz; Rodríguez-Galván, Karen; Manzo-Francisco, Luis Antonio; Vargas‐Alarcón, Gilberto; Fragoso, José Manuel; Peña‐Duque, Marco Antonio; Reyes-Gómez, Carlos Alberto; Martínez-Ríos, Marco Antonio; Peña-Dı́az, Aurora de la

doi:10.1016/j.thromres.2015.08.025

Cited by 22 publications

(15 citation statements)

References 25 publications

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“…Calderon-Cruz et al [13] demonstrated high ontreatment platelet reactivity as a response to clopidogrel among those patients undergoing PCI who were 3435TT homozygotes when compared to the CT/CC individuals [13]. On the other hand, Tang et al [22] showed no statistically significant differences in the platelet response among different C3435T genotypes examining the impact of the variant on the pharmaco dynamic properties of clopidogrel in 670 patients after PCI [22].…”

Section: Discussionmentioning

confidence: 99%

“…The C3435T polymorphism has been associated with altered P-gp activity, the nature of the influence being highly inconsistent across different studies. 8 Although some studies suggested an impact of the 3435TT genotype (mutant T allele being associated with low P-gp expression) on both clopidogrel responsiveness and risk of ACE; other studies reported a worse outcome in patients carrying the wild-type CC genotype [12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Influence of ABCB1 C3435T Genotype on Clinical Cardiovascular Outcomes in Coronary Artery Disease Patients on Clopidogrel Treatment

Vavlukis

Nestorovska

Sterjev

et al. 2017

MOJDDT

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Background: Clopidogrel has been used as a gold standard (alone or in association with aspirin) to prevent vascular complications in atherothrombotic patients undergoing PCI, and as a long-term prevention of cardiovascular events. The drug is subject to efflux via P-glycoprotein (encoded by the ABCB1 gen, also known as MDR1). The ABCB1 C3435T polymorphism may be associated with altered drug metabolism, efficacy and clinical outcome. The aim of this study was to evaluate the influence of ABCB1 C3435T genotype on clinical cardiovascular outcomes in coronary artery disease patients on clopidogrel treatment. Methods:The study included a total of 203 subjects, of which 107 healthy volunteers and 96 patients diagnosed with coronary artery disease on treatment with clopidogrel from the Special Hospital for Surgical Diseases "Filip II". The genotyping of both the control group and the patient group was performed with Real-Time PCR based on the allelic discri mi na tion method. Statistical analysis was performed using SPSS software. The genotype distri butions were assessed for the Hardy-Weinberg equilibrium (HWE) with χ 2 test. Results:The C3435T allele and genotype frequency distribution testing in the patient group showed that the polymorphism is not associated with a risk of atherosclerotic cardiovascular disease (ACD) in the Macedonian population (p>0.05). A higher C-risk allele frequency was found in the subgroup of patients with negative outcome after treatment, compared to the subgroup of patients with positive outcome (0.5568 vs 0.4904; OR=1.306 T→C; p=0.35855). The same trend was observed when following the C3435T allele and genotype distribution in the subgroup of patients with normal CYP2C19 genetic status (CYP2C19*1/*1) (0.6400 vs 0.4868; OR=1.874 T→C; p=0.09105). Conclusion:The results indicate that the ABCB1 C3435T polymorphism is an independent and complementary genetic factor that affects the outcome of clopidogrel treatment, but requires further research and a bigger study population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of ABCB1 C3435T Genotype on Clinical Cardiovascular Outcomes in Coronary Artery Disease Patients on Clopidogrel Treatment

Vavlukis

Nestorovska

Sterjev

et al. 2017

MOJDDT

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“…Генотип ТТ гена ABCB1 (в позиции 3435) приводит к снижению всасывания препарата по сравнению с генотипом СС [24]. Исследования, описывающие влияние указанного полиморфизма на активность тромбоцитов, неоднозначны [24][25][26][27][28][29]. Данные французского регистра FAST-MI продемонстрировали увеличение частоты неблагоприятных событий у носителей полиморфного аллеля по сравнению с генотипом СС [25], так же как и исследование Simon c соавт.…”

Section: клопидогрелunclassified

“…Исследования, описывающие влияние указанного полиморфизма на активность тромбоцитов, неоднозначны [24][25][26][27][28][29]. Данные французского регистра FAST-MI продемонстрировали увеличение частоты неблагоприятных событий у носителей полиморфного аллеля по сравнению с генотипом СС [25], так же как и исследование Simon c соавт. [26] Однако эти данные не воспроизводились в метаанализе [27], включившем в себя более 19000 пациентов, где не было показало влияния полиморфизма гена ABCB1 на развитие клинических исходов (инфаркт миокарда, тромбоз стента, инсульт).…”

Section: клопидогрелunclassified

Pharmacogenetics of Antithrombotic Drugs: Status Update on the Problem

Кропачева

2018

Aterotromboz

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The review deals with the main trials devoted to the study of genetic markers of individual variability in drug response to antithrombotic agents. The first part describes the studies of the genes encoding the platelet receptor subunits studied in the association of the possible insufficient effect of acetylsalicylic acid, and transporter proteins and allelic variants with reduced CYP450 functional activity, which are associated with insufficient effect on clopidogrel therapy. The second part considers polymorphisms that determine the individual dose and the risk of bleeding due to excessive hypocoagulation in patients taking warfarin. It also presents current data on the study of genetically determined individual reactions to the new inhibitors: P2Y12 inhibitors (prasugrel and ticagrelor) and direct oral anticoagulants.

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“…122 This observation has been reported in reviews by other investigators. 75,123,124 Genetics and drug targets…”

Section: Decreased Effectmentioning

confidence: 99%

Utilisation de la pharmacogénomique et de la pharmacogénétique à l’unité de soins intensifs: un compte rendu narratif

MacKenzie

Hall

2016

Can J Anesth/J Can Anesth

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C3435T polymorphism of the ABCB1 gene is associated with poor clopidogrel responsiveness in a Mexican population undergoing percutaneous coronary intervention

Cited by 22 publications

References 25 publications

Influence of ABCB1 C3435T Genotype on Clinical Cardiovascular Outcomes in Coronary Artery Disease Patients on Clopidogrel Treatment

Influence of ABCB1 C3435T Genotype on Clinical Cardiovascular Outcomes in Coronary Artery Disease Patients on Clopidogrel Treatment

Pharmacogenetics of Antithrombotic Drugs: Status Update on the Problem

Utilisation de la pharmacogénomique et de la pharmacogénétique à l’unité de soins intensifs: un compte rendu narratif

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