The association of polymorphisms in related circadian rhythm genes and clopidogrel resistance susceptibility

Su, Jia; Yu, Qinglin; Yang, Ji-Hyuk; Zheng, Nan; Zhong, Jinyan; Ji, Li; Li, Jiyi; Chen, Xiaomin

doi:10.1111/bcpt.13622

Cited by 3 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…From 2013 to 2018, through platelet function evaluation by VerifyNow ® P2Y12, 63 ACS patients whose ARU were >550 were defined as the existence of AR. Among these patients, 45 persons who met the requirements [10] were recruited for present investigation. These patients were divided randomly into control group (group A, 22 patients) and treatment group (group B, 23 patients).…”

Section: Resultsmentioning

confidence: 99%

Impact of Xuefu Zhuyu Decoction on Reducing Hyporesponsiveness of Aspirin in Acute Coronary Syndrome

Yu,

Zhu,

Sun

et al. 2024

IJPS

View full text Add to dashboard Cite

The main objective of this study is to evaluate the effect of Xuefu Zhuyu decoction on aspirin resistance in acute coronary syndrome patients. We enrolled 45 patients with aspirin resistance and divided them randomly into control group (group A) and treatment group (group B). We applied Xuefu Zhuyu decoction to the group B for 4 w. Before treatment and after 4 w of treatment, we evaluated the platelet reactivity, and performed biochemical and molecular biology analyses from both subgroups. Through logistic regression analysis, we assessed the association between improvement of platelet function and confounding factors. Lastly, clinical follow-ups for 1 mo and 12 mo were performed to analysis the therapeutic effects. We found the aspirin reaction unit was clearly on decline 602.35±26.49 vs. 542.48±43.09 (before treatment vs. after treatment; p<0.001) in group B. Through quantitative reverse transcription-polymerase chain reaction and radioimmunoassay, we assessed the expression of cyclooxygenase-1 and thromboxane A2, and the results indicated that after treatment, the thromboxane A2 decreased 503.4±12.0 vs. 447.8±48.5 (before treatment vs. after treatment; p<0.001). In group B, hemorheology improved significantly, and plasma viscosity, whole blood viscosity along with fibrinogen decreased significantly (all p<0.01). Meanwhile, in group B, the glucose was correlated with aspirin reaction unit and the expression of thromboxane A2 was a protective factor of aspirin reaction unit, and aspirin resistance patients would suffer less major adverse cardiac events (p=0.024). Xuefu Zhuyu decoction might reduce hyporesponsiveness of aspirin by inhibiting thromboxane A2 and improve the hemorheological index, which are of great significance for the prevention in cardiovascular events.

show abstract

Section: Resultsmentioning

confidence: 99%

Impact of Xuefu Zhuyu Decoction on Reducing Hyporesponsiveness of Aspirin in Acute Coronary Syndrome

Yu,

Zhu,

Sun

et al. 2024

IJPS

View full text Add to dashboard Cite

show abstract

“…Although Clock regulates the circadian expression of P-gp (Murakami et al, 2008), P-gp may not contribute to clopidogrel chronoefficacy because P-gp does not transport clopidogrel in mice and in recombinant inverted membrane vesicles overexpressing human P-gp (Ji et al, 2021). These findings help to explain the attention that the mRNA expression of CLOCK is positively associated with susceptibility to clopidogrel resistance in humans (majorly attributed to differences in metabolism), further illustrating the crucial role of CLOCK in regulation of clopidogrel efficacy (Su et al, 2021).…”

Section: Clock Regulates Cyp1a2 Cyp3a11 and Ces1d Expressions In Hepa...mentioning

confidence: 89%

Role of circadian clock in the chronoefficacy and chronotoxicity of clopidogrel

et al. 2023

British J Pharmacology

View full text Add to dashboard Cite

Background and PurposeThe role of circadian locomotor output cycles kaput (CLOCK) in regulating drug chronoefficacy and chronotoxicity remains elusive. Here, we aimed to uncover the impact of CLOCK and dosing time on clopidogrel efficacy and toxicity.Experimental ApproachThe antiplatelet effect, toxicity and pharmacokinetics experiments were conducted with Clock−/− mice and wild‐type mice, after gavage administration of clopidogrel at different circadian time points. The expression levels of drug‐metabolizing enzymes were determined by quantitative polymerase chain reaction (qPCR) and western blotting. Transcriptional gene regulation was investigated using luciferase reporter and chromatin immunoprecipitation assays.Key ResultsThe antiplatelet effect and toxicity of clopidogrel in wild‐type mice showed a dosing time‐dependent variation. Clock ablation reduced the antiplatelet effect of clopidogrel, but increased clopidogrel‐induced hepatotoxicity, with attenuated rhythms of clopidogrel active metabolite (Clop‐AM) and clopidogrel, respectively. We found that Clock regulated the diurnal variation of Clop‐AM formation by modulating the rhythmic expression of CYP1A2 and CYP3A1, and altered clopidogrel chronopharmacokinetics by regulation of CES1D expression. Mechanistic studies revealed that CLOCK activated Cyp1a2 and Ces1d transcription by directly binding to the enhancer box (E‐box) elements in their promoters, and promoted Cyp3a11 transcription through enhancing the transactivation activity of albumin D‐site‐binding protein (DBP) and thyrotroph embryonic factor (TEF).Conclusions and ImplicationsCLOCK regulates the diurnal rhythmicity in clopidogrel efficacy and toxicity through regulation of CYP1A2, CYP3A11 and CES1D expression. These findings may contribute to optimizing dosing schedules for clopidogrel and may deepen understanding of the circadian clock and chronopharmacology.

show abstract

“…SNPs in Circadian Locomotor Output Cycles Kaput ( CLOCK ), Cryptochrome Circadian Regulator 1 ( CRY1 ), Calcium Voltage-Gated Channel Subunit Alpha1 C ( CACNA1C ), and Protein Kinase C Gamma ( PRKCG ) affect platelet activity in clopidogrel-treated patients via the circadian rhythm system, according to Su et al 2021. 62 The circadian rhythm system keeps track of the body cycle time and serves as the foundation for physiological and biochemical tasks. Circadian rhythm genes have a role in several heart-related disorders.…”

Section: Discussionmentioning

confidence: 99%

The Potential of Single Nucleotide Polymorphisms (SNPs) as Biomarkers and Their Association with the Increased Risk of Coronary Heart Disease: A Systematic Review

Sitinjak,

Murdaya,

Rachman

et al. 2023

VHRM

View full text Add to dashboard Cite

Human genetic analyses and epidemiological studies showed a potential association between several types of gene polymorphism and the development of coronary heart disease (CHD). Many studies on this pertinent topic need to be investigated further to reach an evidence-based conclusion. Therefore, in this current review, we describe several types of gene polymorphisms that are potentially linked to CHD. A systematic review using the databases EBSCO, PubMed, and ScienceDirect databases was searched until October of 2022 to find relevant studies on the topic of gene polymorphisms on risk factors for CHD, especially for the factors associated with single nucleotide polymorphisms (SNPs). The risk of bias and quality assessment was evaluated by Joanna Briggs Institute (JBI) guidelines. From keyword search results, a total of 6243 articles were identified, which were subsequently narrowed to 14 articles using prespecified inclusion criteria. The results suggested that there were 33 single nucleotide polymorphisms (SNPs) that can potentially increase the risk factors and clinical symptoms of CHD. This study also indicated that gene polymorphisms had a potential role in increasing CHD risk factors that were causally associated with atherosclerosis, increased homocysteine, immune/inflammatory response, Low-Density Lipoprotein (LDL), arterial lesions, and reduction of therapeutic effectiveness. In conclusion, the findings of this study indicate that SNPs may increase risk factors for CHD and SNPs show different effects between individuals. This demonstrates that knowledge of SNPs on CHD risk factors can be used to develop biomarkers for diagnostics and therapeutic response prediction to decide successful therapy and become the basis for defining personalized medicine in future.

show abstract

The association of polymorphisms in related circadian rhythm genes and clopidogrel resistance susceptibility

Cited by 3 publications

References 40 publications

Impact of Xuefu Zhuyu Decoction on Reducing Hyporesponsiveness of Aspirin in Acute Coronary Syndrome

Impact of Xuefu Zhuyu Decoction on Reducing Hyporesponsiveness of Aspirin in Acute Coronary Syndrome

Role of circadian clock in the chronoefficacy and chronotoxicity of clopidogrel

The Potential of Single Nucleotide Polymorphisms (SNPs) as Biomarkers and Their Association with the Increased Risk of Coronary Heart Disease: A Systematic Review

Contact Info

Product

Resources

About