scholarly journals Association ofP2Y12Gene Promoter DNA Methylation with the Risk of Clopidogrel Resistance in Coronary Artery Disease Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Jia Su ◽  
Xiaojing Li ◽  
Qinglin Yu ◽  
Yahui Liu ◽  
Yaqing Wang ◽  
...  

Background. Clopidogrel inhibits the ADP receptorP2Y12to keep down the platelet aggregation. The goal of our study is to investigate the contribution ofP2Y12promoter DNA methylation to the risk of clopidogrel resistance (CR).Methods. The platelet functions were measured by the VerifyNowP2Y12assay. Applying the bisulfite pyrosequencing technology, DNA methylation levels of two CpG dinucleotides onP2Y12promoter were tested among 49 CR cases and 57 non-CR controls. We also investigated the association amongP2Y12DNA methylation, various biochemical characteristics, and CR.Result. Lower methylation of two CpGs indicated the poorer clopidogrel response (CpG1,P=0.009; CpG2,P=0.022) in alcohol abusing status. Meanwhile CpG1 methylation was inversely correlated with CR in smoking patients (P=0.026) and in subgroup of Albumin < 35 (P=0.002). We observed that the level of DNA methylation might be affected by some clinical markers, such as TBIL, LEVF, Albumin, AST. The results also showed that the quantity of stent, fasting blood-glucose, and lower HbAC1 were the predictors of CR.Conclusions. The evidence from our study indicates thatP2Y12methylation may bring new hints to elaborate the pathogenesis of CR.

Epigenetics ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. 464-472 ◽  
Author(s):  
Simon-Pierre Guay ◽  
Diane Brisson ◽  
Johannie Munger ◽  
Benoit Lamarche ◽  
Daniel Gaudet ◽  
...  

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 622
Author(s):  
Omeima Abdullah ◽  
Ziad Omran ◽  
Salman Hosawi ◽  
Ali Hamiche ◽  
Christian Bronner ◽  
...  

Silencing of tumor suppressor genes (TSGs) through epigenetic mechanisms, mainly via abnormal promoter DNA methylation, is considered a main mechanism of tumorigenesis. The abnormal DNA methylation profiles are transmitted from the cancer mother cell to the daughter cells through the involvement of a macromolecular complex in which the ubiquitin-like containing plant homeodomain (PHD), and an interesting new gene (RING) finger domains 1 (UHRF1), play the role of conductor. Indeed, UHRF1 interacts with epigenetic writers, such as DNA methyltransferase 1 (DNMT1), histone methyltransferase G9a, erasers like histone deacetylase 1 (HDAC1), and functions as a hub protein. Thus, targeting UHRF1 and/or its partners is a promising strategy for epigenetic cancer therapy. The natural compound thymoquinone (TQ) exhibits anticancer activities by targeting several cellular signaling pathways, including those involving UHRF1. In this review, we highlight TQ as a potential multitarget single epidrug that functions by targeting the UHRF1/DNMT1/HDAC1/G9a complex. We also speculate on the possibility that TQ might specifically target UHRF1, with subsequent regulatory effects on other partners.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianfeng Xu ◽  
Jiejun Shi ◽  
Xiaodong Cui ◽  
Ya Cui ◽  
Jingyi Jessica Li ◽  
...  

AbstractPromoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.


2010 ◽  
Vol 42 (12) ◽  
pp. 1093-1100 ◽  
Author(s):  
Julie Borgel ◽  
Sylvain Guibert ◽  
Yufeng Li ◽  
Hatsune Chiba ◽  
Dirk Schübeler ◽  
...  

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