Associations of <i>PER3</i> polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel

Zheng, Nan; Yin, Fengying; Yu, Qinglin; Zhong, Jinyan; Yang, Ji-Hyuk; Xu, Zhifeng; Su, Jia; Chen, Xiaomin

doi:10.1002/jcla.23713

Cited by 4 publications

(5 citation statements)

References 44 publications

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“…The PERIOD3 (PER3) as the rhythm regulation gene was proved helpful to assess the clopidogrel resistance. 39 Other SNPs have been confirmed to be related…”

Section: Discussionmentioning

confidence: 99%

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Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population

Zhong

Zheng

et al. 2021

Clinical Laboratory Analysis

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Background: Due to the loss of responsiveness to insulin, diabetes mellitus (DM) patients develop increased platelet reactivity and reduced response to antiplatelet agents. Nevertheless, the relationship between the single-nucleotide polymorphisms (SNP) of the signal pathway gene of insulin secretion and the effect of clopidogrel is elusive.Methods: Blood samples were collected from patients administered with dualantiplatelet therapy (clopidogrel, 75 mg, once daily and aspirin, 100 mg, once daily) after 5 days and completed test within 4 h. The VerifyNow P2Y12 assay was used to measure the platelet functions, and the results were expressed as a P2Y12 reaction unit (PRU). Notably, the selected SNPs were analyzed to demonstrate the functionality of genetic variants.Results: Analysis of the study population showed that old age, lower plasma albumin (ALB) level, higher creatinine (CREA) level, higher uric acid (UA) level, lower platelet (PLT) count, and lower plateletcrit (PCT) potentially increased the risk of clopidogrel resistance. In a single-nucleotide polymorphism rs6056209 of the PCLB1 gene, the AG genotype was a risk factor for clopidogrel resistance (p < 0.05, OR = 1.574).Similarly, the CC and AG genotype in GNAS rs7121 and CCKAR rs1800857 were protective factors (p < 0.05, OR = 0.094; p <0.05, OR = 0.491). TT was a protective factor in rs10814274 of the CREB3 gene (p < 0.05, OR = 0.444). In the RAPGEF4 gene polymorphism rs17746510, TG was the protective genotype, and the TT genotype was a risk factor for clopidogrel resistance. GCG rs5645 was confirmed; there was a relationship between genotypes containing A or G and clopidogrel resistance. Conclusion:Single-nucleotide polymorphisms of insulin secretion signaling pathway genes trigger clopidogrel resistance.

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“…The PERIOD3 (PER3) as the rhythm regulation gene was proved helpful to assess the clopidogrel resistance. 39 Other SNPs have been confirmed to be related…”

Section: Discussionmentioning

confidence: 99%

“…The PERIOD3 (PER3) as the rhythm regulation gene was proved helpful to assess the clopidogrel resistance. 39 Other SNPs have been confirmed to be related to clopidogrel resistance; however, their reasons and mechanisms are unclear.…”

Section: Discussionmentioning

confidence: 99%

Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population

Zhong

Zheng

et al. 2021

Clinical Laboratory Analysis

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“…12,13 The COSTIC study conducted 2018 proposed that the Chinese population had more obvious clinical benefits from clopidogrel. Clopidogrel resistance is affected by a variety of clinical factors, including diabetes, 14 chronic kidney disease, 15 smoking, 16 drug interactions (such as proton pump inhibitors), 17 circadian rhythm, 18 age, inflammation, reduced left ventricular ejection fraction, and body mass index. 19 Among them, diabetes mellitus (DM) had the most significant effect on clopidogrel's low response.…”

Section: Discussionmentioning

confidence: 99%

The DNAm levels of CREB5 (cg11301281) were associated with clopidogrel resistance

Yang

Yu³

et al. 2022

Clinical Laboratory Analysis

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Purpose Clopidogrel resistance (CR) is mostly caused by interindividual variability of the platelet inhibition of clopidogrel, which may induce cardiovascular events. The aim of this research was to evaluate whether DNAm levels of CREB5 (cg01534253) are involved in CR among acute coronary syndrome (ACS) patients treated with clopidogrel. Methods 72 patients(36 CR and 36 non‐CR) who underwent ACS were included in this study. The VerifyNow P2Y12 assay was selected to evaluate residual platelet reactivity, and bisulfite pyrosequencing methods was used to examine DNA methylation levels on cg01534253. Secondly, CREB5 mRNA expression was analyzed via quantitative real‐time PCR. Last, we employed logistic regression to test the interaction between genetic factors of CREB5 methylation and multiple clinical variables in CR patients. Results Subunit analysis indicated that for patients whose HbA1c levels were ≥6.5% or whose GLU levels were ≥7 mmol/L, lower methylation of cg01534253 indicated a poorer clopidogrel response. In addition, CREB5 mRNA expression was increased in CR patients with GLU levels ≥7 mmol/L. Moreover, regression analysis indicated that the values of albumin and uric acid were correlated with the incidence of CR. Conclusions Our findings were likely to provide fresh understanding for the new mechanism of platelet inhibition failure and promote individualized antiplatelet therapy.

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“…At present, there is no uniform standard for the definition of CR. Common concepts include clinical CR and laboratory CR 20,21 . Clinical CR is generally considered to be that thromboembolic events still occur under standard clopidogrel treatment.…”

Section: Methodsmentioning

confidence: 99%

“…Common concepts include clinical CR and laboratory CR. 20,21 Clinical CR is generally considered to be that thromboembolic events still occur under standard clopidogrel treatment. The laboratory CR is identified by the results of platelet function testing.…”

Section: Platelet Functionmentioning

confidence: 99%

The expression profile of platelet‐derived miRNA in coronary artery disease patients with clopidogrel resistance

Lin

et al. 2021

Pharmacology Res & Perspec

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Associations of PER3 polymorphisms with clopidogrel resistance among Chinese Han people treated with clopidogrel

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 4 publications

References 44 publications

Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population

Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population

The DNAm levels of CREB5 (cg11301281) were associated with clopidogrel resistance

The expression profile of platelet‐derived miRNA in coronary artery disease patients with clopidogrel resistance

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