microRNA-605 rs2043556 polymorphisms affect clopidogrel therapy through modulation of CYP2B6 and P2RY12 in acute coronary syndrome patients

Zhou, Wan-Lu; Mo, Zhenzhen; Xiao, Fang; Dai, Wei; Guo, Wei; Zhang, Gan; Zhang, Wei; Chen, Bilian

doi:10.1080/09537104.2019.1696455

Cited by 7 publications

(6 citation statements)

References 45 publications

(54 reference statements)

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“…ACS was diagnosed according to the 2007 ACC/AHA guidelines [21]. The exclusion criteria have been described in our previous study [20]. We defined the bleeding events based on the criteria of the Bleeding Academic Research Consortium (BARC), mainly consisting of type 2, 3, or 5 [22].…”

Section: Population With Acsmentioning

confidence: 99%

“…MicroRNAs (miRNAs) are endogenous, singlestranded small noncoding RNAs that have emerged as important regulators of target gene expression by degrading mRNAs or inhibiting mRNA translation [16,17]. It has been found that some miRNAs may facilitate the diagnosis of ACS [18] and that polymorphisms of miR-NAs may affect the function of the target genes [19,20].…”

Section: Introductionmentioning

confidence: 99%

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miR-6076 rs1463411 polymorphisms are associated with bleeding during clopidogrel treatment in patients with acute coronary syndrome

Yuan

Peng

et al. 2023

Eur J Med Res

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Bleeding is a major adverse event during clopidogrel treatment in patients with acute coronary syndrome (ACS). However, the potential mechanism affecting bleeding among individuals is unclear. Herein, we investigated the involvement of CYP2C19*2 and CYP2C19*3, as well as 10 miRNA polymorphisms, in bleeding in Chinese patients with ACS during the first year of clopidogrel treatment. The miR-6076 rs1463411 G polymorphism was significantly associated with the risk of bleeding (P < 0.001), and the rs1463411 GT + GG genotype significantly increased the risk of bleeding (adjusted odds ratio, 6.09; 95% confidence interval, 1.09–34.0; P < 0.001). Dual luciferase assay showed that miR-6076 significantly decreased the mRNA expression of P2RY12 (P < 0.05). P2RY12 mRNA and protein levels were significantly lower in cells transfected with miR-6076-G than in cells transfected with miR-6076-T (P < 0.05). The findings indicate that miR-6076 targets P2RY12 mRNA and that miR-6076 rs1463411 T/G polymorphisms differentially regulate P2RY12 mRNA and protein levels in cells. rs1463411 G polymorphism may increase the risk of bleeding during clopidogrel treatment in patients with ACS.

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Section: Population With Acsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-6076 rs1463411 polymorphisms are associated with bleeding during clopidogrel treatment in patients with acute coronary syndrome

Yuan

Peng

et al. 2023

Eur J Med Res

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“…Moreover, patients that were carriers of two CYP2C19 loss of function (LOF) alleles had a significantly increased risk of ST and AMI when compared to only one LOF carrier or non-carrier. This phenomenon may be caused by the reduced enzymes activity in CYP2C19 * 2 and CYP2C19 * 3 LOF polymorphisms carriers, impaired conversion of clopidogrel into an active metabolite, and, what follows, insufficient P2Y 12 inhibition (Zhou et al, 2020).…”

Section: Platelet-derived Mirna and Genetic Variability In Antiplatelet Treatmentmentioning

confidence: 99%

“…ACS patients with miR-605-G allelic variant present less AMI and unstable angina (UA) when compared to miR-605-A allelic patients, after 1 year of clopidogrel treatment, which may be due to lesser inhibition of CYP2B6. It is hypothesized that normal expression of P2Y 12 receptors in miR-605-G allelic variant individuals is related to a better response to antiplatelet treatment because the appropriate amount of active drug can bind to the normal number of ADP receptors (Zhou et al, 2020).…”

Section: Platelet-derived Mirna and Genetic Variability In Antiplatelet Treatmentmentioning

confidence: 99%

MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review

et al. 2021

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MicroRNAs (miRNAs) are small, non-coding RNAs, able to regulate cellular functions by specific gene modifications. Platelets are the major source for circulating miRNAs, with significant regulatory potential on cardiovascular pathophysiology. MiRNAs have been shown to modify the expression of platelet proteins influencing platelet reactivity. Circulating miRNAs can be determined from plasma, serum, or whole blood, and they can be used as diagnostic and prognostic biomarkers of platelet reactivity during antiplatelet therapy as well as novel therapeutic targets in cardiovascular diseases (CVDs). Herein, we review diagnostic and prognostic value of miRNAs levels related to platelet reactivity based on human studies, presenting its interindividual variability as well as the substantial role of genetics. Furthermore, we discuss antiplatelet treatment in the context of miRNAs alterations related to pathways associated with drug response.

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“…20 And micro-RNAs are described in literature as such potential biomarkers. [21][22][23][24][25] These micro-RNAs are small non-coding sequences of nucleotides which bind to mRNA sites and block transcription. This causes a decrease in the production of protein.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction

Rytkin¹,

Мирзаев²,

Bure³

et al. 2021

PGPM

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The aim of this study is to assess 6 micro-RNAs: miR-126, miR-223, miR-150, miR-29, miR-34, miR-142 as potential biomarkers for P2Y12-inhibitors resistance prediction. Methods: Eighty patients with an acute coronary syndrome undergoing percutaneous coronary intervention treated in a multidisciplinary hospital in Moscow with DAPT (either with ticagrelor, n=45, or clopidogrel, n=35) were enrolled. The carriership of 6 clinically relevant polymorphisms for ticagrelor and 17 for clopidogrel was detected. Expression levels of six prospective miRNAs were measured. The activity of CYP3A4 isoenzyme was measured as the ratio of the concentrations of cortisol and 6β-hydroxycortisol. Results:The polymorphisms of the P2Y12-inhibitors ADME genes that demonstrated statistically significant connection with miRNA expression levels are as follows: P2Y12R (A>G, rs3732759) and miR-29 (p=0.017), miR-34 (p=0.003); CYP2C19*17 (C-806T, rs1224856) and miR-142 (p=0.012); PON1 (Q192R, rs662) and miR-29 (p=0.004), ABCG2 (G>T, rs2231142) and miR-34 (p=0.007). MiRNAs expression levels showed connection with the results of the platelet reactivity assessment by utilizing VerifyNow assay ("Instrumentation laboratory", MA, US). MiR-126 (β coefficient=−0.076, SE=0.032, p=0.021), miR-223 (β coefficient=−0.089, SE=0.041, p=0.032), miR-29 (β coefficient=−0.042, SE=0.018, p=0.026), miR-142 (β coefficient=−0.072, SE=0.026, p=0.008) have the potential to be used as biomarkers and may substitute platelet reactivity testing. Conclusion:This study has revealed new biomarkers for P2Y12-inhibitors resistance testing: miR-29, miR-34, miR-126, miR-142, miR-223.

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microRNA-605 rs2043556 polymorphisms affect clopidogrel therapy through modulation of CYP2B6 and P2RY12 in acute coronary syndrome patients

Abstract: View related articles View Crossmark data Citing articles: 1 View citing articles microRNA-605 rs2043556 polymorphisms affect clopidogrel therapy through modulation of CYP2B6 and P2RY12 in acute coronary syndrome patients

Cited by 7 publications

References 45 publications

miR-6076 rs1463411 polymorphisms are associated with bleeding during clopidogrel treatment in patients with acute coronary syndrome

miR-6076 rs1463411 polymorphisms are associated with bleeding during clopidogrel treatment in patients with acute coronary syndrome

MicroRNA as Potential Biomarkers of Platelet Function on Antiplatelet Therapy: A Review

MicroRNAs as Novel Biomarkers for P2Y12 – Inhibitors Resistance Prediction

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