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Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans

Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared...

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Autores principales: Yang, Jin, Yu, Qinglin, Xu, Zhifeng, Zheng, Nan, Zhong, Jinyan, Li, Jiyi, Liu, Yahui, Xu, Hongyu, Su, Jia, Ji, Lindan, Chen, Xiaomin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844369/
https://www.ncbi.nlm.nih.gov/pubmed/33519892
http://dx.doi.org/10.3389/fgene.2020.583215
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author Yang, Jin
Yu, Qinglin
Xu, Zhifeng
Zheng, Nan
Zhong, Jinyan
Li, Jiyi
Liu, Yahui
Xu, Hongyu
Su, Jia
Ji, Lindan
Chen, Xiaomin
author_facet Yang, Jin
Yu, Qinglin
Xu, Zhifeng
Zheng, Nan
Zhong, Jinyan
Li, Jiyi
Liu, Yahui
Xu, Hongyu
Su, Jia
Ji, Lindan
Chen, Xiaomin
author_sort Yang, Jin
collection PubMed
description Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared the whole genomic methylation patterns of blood samples from patients with CR (n = 6) and non-CR (n = 6) with the Human Methylation 850K BeadChip assay. We explored differentially methylated CpG sites, genes, and pathways using bioinformatics profiling. The CR and control groups showed significantly different DNA methylation at 7,098 sites, with 979 sites showing hypermethylation and 6,119 sites showing hypomethylation. The pyrosequencing method was used to validate four differentially methylated CpG loci (cg23371584, cg15971518, cg04481923, cg22507406), confirming that DNA methylation was associated with the risk of CR (30 CR vs. 30 non-CR). The relative mRNA expression of the four genes (BTG2, PRG2, VTRNA2-1, PER3) corresponding to the loci above was also associated with CR, suggesting that alterations in DNA methylation may affect the expression of these four genes, eventually resulting in CR. Additionally, differentially methylated sites are partially related to genes and pathways that play key roles in process of circadian entrainment, insulin secretion, and so on. Hence, the mechanism and biological regulation of CR might be reflected through these epigenetic alterations, but future research will need to address the causal relationships.
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spelling pubmed-78443692021-01-30 Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans Yang, Jin Yu, Qinglin Xu, Zhifeng Zheng, Nan Zhong, Jinyan Li, Jiyi Liu, Yahui Xu, Hongyu Su, Jia Ji, Lindan Chen, Xiaomin Front Genet Genetics Antiplatelet therapy has become a cornerstone in the treatment of coronary heart disease (CHD). However, due to high-residual-platelet-reactivity, clopidogrel resistance (CR) is a common phenomenon, and it is rarely known about the relationship between CR and epigenetic changes. This study compared the whole genomic methylation patterns of blood samples from patients with CR (n = 6) and non-CR (n = 6) with the Human Methylation 850K BeadChip assay. We explored differentially methylated CpG sites, genes, and pathways using bioinformatics profiling. The CR and control groups showed significantly different DNA methylation at 7,098 sites, with 979 sites showing hypermethylation and 6,119 sites showing hypomethylation. The pyrosequencing method was used to validate four differentially methylated CpG loci (cg23371584, cg15971518, cg04481923, cg22507406), confirming that DNA methylation was associated with the risk of CR (30 CR vs. 30 non-CR). The relative mRNA expression of the four genes (BTG2, PRG2, VTRNA2-1, PER3) corresponding to the loci above was also associated with CR, suggesting that alterations in DNA methylation may affect the expression of these four genes, eventually resulting in CR. Additionally, differentially methylated sites are partially related to genes and pathways that play key roles in process of circadian entrainment, insulin secretion, and so on. Hence, the mechanism and biological regulation of CR might be reflected through these epigenetic alterations, but future research will need to address the causal relationships. Frontiers Media S.A. 2021-01-15 /pmc/articles/PMC7844369/ /pubmed/33519892 http://dx.doi.org/10.3389/fgene.2020.583215 Text en Copyright © 2021 Yang, Yu, Xu, Zheng, Zhong, Li, Liu, Xu, Su, Ji and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Yang, Jin
Yu, Qinglin
Xu, Zhifeng
Zheng, Nan
Zhong, Jinyan
Li, Jiyi
Liu, Yahui
Xu, Hongyu
Su, Jia
Ji, Lindan
Chen, Xiaomin
Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans
title Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans
title_full Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans
title_fullStr Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans
title_full_unstemmed Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans
title_short Clopidogrel Resistance Is Associated With DNA Methylation of Genes From Whole Blood of Humans
title_sort clopidogrel resistance is associated with dna methylation of genes from whole blood of humans
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844369/
https://www.ncbi.nlm.nih.gov/pubmed/33519892
http://dx.doi.org/10.3389/fgene.2020.583215
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