DNA methylation biomarkers of myocardial infarction and cardiovascular disease

Fernández‐Sanlés, Alba; Sayols-Baixeras, Sergi; Subirana, Isaac; Sentı́, Mariano; Pérez‐Fernández, Silvia; Moura, Manuel de Castro; Esteller, Manel; Marrugat, Jaume; Elosúa, Roberto

doi:10.1186/s13148-021-01078-6

Cited by 52 publications

(38 citation statements)

References 41 publications

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“…The calibration and DCA plots also showed the very good fit of the model. Similar to previous findings (18,28), the model showed that methylation was an important molecular change in the development of AMI. Under the model, the 5 most important genes were FTO, WTAP, YTHDC1, IGFBP3, and CBLL1.…”

Section: Discussionsupporting

confidence: 87%

Diagnosis, clustering, and immune cell infiltration analysis of m6A-related genes in patients with acute myocardial infarction—a bioinformatics analysis

Liang¹,

Wang²,

Zhang³

et al. 2022

J Thorac Dis

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Background: Accurate myocardial infarction (AMI) is one of the leading causes of mortality worldwide.N6-methyladenosine (m6A) modification plays an important role in the development of cardiac remodeling and the cardiomyocyte contractile function. The aim of this study is to analyze the m6A-related molecular biological mechanisms of AMI in terms of accurate diagnosis and prognosis. Methods:The platform data and probe data of the GSE66360 data set were downloaded. The differential analysis was conducted by combining the m6A-related gene expression. Thereafter, a diagnostic model was established using the random-forest method. The diagnostic accuracy of the diagnostic models was assessed by using the area under the receiver operating characteristic (ROC) curve (AUC). Next, the patients with AMI were clustered by unsupervised machine learning using the R software. Finally, an immune cell clustering analysis for each cluster was conducted to determine the correlations between m6A-related gene expression and the infiltration amount of the immune cells. The case and control groups were not matched in terms of demographics.Results: The GSE6636 data set comprised 99 participants (49 patients with AMI and 50 without in control group). The differential analysis identified 10 m6A-related genes: 5 writers [Methyltransferaselike 3 (METTL3), Methyltransferase-like 14 (METTL14), Wilms tumor 1-associated protein (WTAP), Zinc Finger CCCH-Type Containing 13 (ZC3H13), and Casitas B-lineage proto-oncogene like 1 (CBLL1)],4 readers [YT521-B homology domain-containing family 3 (YTHDF3), Fragile X mental retardation type 1 (FMR1), YT521-B homology-domain-containing protein 1 (YTHDC1), and insulin-like growth factor binding protein 3 (IGFBP3)] and 1 eraser [fat mass and obesity associated (FTO) gene]. The Mean Decrease Gini (MDG) values of these 10 genes were greater than 2. The FTO, WTAP, YTHDC1, IGFBP3, and CBLL1were included in the model with a C index of 0.842. METTL3, ZC3H13, WTAP, and CBLL1 were highly expressed in Type A, and YTHDF3 was highly expressed in Type B.Conclusions: A diagnostic model of AMI was established based on the genes of FTO, WTAP, YTHDC1, IGFBP3, and CBLL1. Additionally, 2 molecular subtypes were successfully identified from the abovementioned gene. Our findings could provide a novel method for the accurate diagnosis of AMI.

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Section: Discussionsupporting

confidence: 87%

Diagnosis, clustering, and immune cell infiltration analysis of m6A-related genes in patients with acute myocardial infarction—a bioinformatics analysis

Liang¹,

Wang²,

Zhang³

et al. 2022

J Thorac Dis

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“…Studies have revealed the complementary expression patterns of lipid metabolism, calcium regulation, and methylation of related genes in peripheral blood leucocyte samples of patients with MI (Agha et al, 2019). These CpGs sites and genes stress the correlation of ion regulation, lipid metabolism, and inflammation in the MI biological mechanisms (Fernández-Sanlés et al, 2021). Thus, the new DNA methylation sequencing technology can identify potential target sites related to the aberrant epigenetic regulation of MI (Koseler et al, 2020).…”

Section: Dna Methylation and MImentioning

confidence: 99%

Targeting Epigenetics and Non-coding RNAs in Myocardial Infarction: From Mechanisms to Therapeutics

Chen¹,

Liu²,

Ma³

et al. 2021

Front. Genet.

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Myocardial infarction (MI) is a complicated pathology triggered by numerous environmental and genetic factors. Understanding the effect of epigenetic regulation mechanisms on the cardiovascular disease would advance the field and promote prophylactic methods targeting epigenetic mechanisms. Genetic screening guides individualised MI therapies and surveillance. The present review reported the latest development on the epigenetic regulation of MI in terms of DNA methylation, histone modifications, and microRNA-dependent MI mechanisms and the novel therapies based on epigenetics.

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“…Epigenetics data, especially DNA methylation, are a promising way to understand molecular mechanisms of diseases. A few studies have paid attention to the connection between DNA methylation and AMI [ 8 – 10 ].…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of DNA methylation and gene expression reveals key molecular signatures in acute myocardial infarction

Luo

Shen

et al. 2022

Clin Epigenet

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Backgrounds Acute myocardial infarction (AMI) has been one of the most fatal diseases among all types of heart diseases due to its rapid onset and high rates of fatality. Understanding accurately how multi-omics molecular features change at the early stage of AMI is crucial for its treatment. Currently, the changes involved in DNA methylation modification and gene expression of multiple genes have remained unexplored. Results We used the RNA-seq and MeDIP-seq on heart tissues from AMI mouse models at series of time points (Sham, AMI 10-min, 1-h, 6-h, 24-h and 72-h), to comprehensively describe the transcriptome and genome-wide DNA methylation changes at above time points. We identified 18814, 18614, 23587, 26018 and 33788 differential methylation positions (DMPs) and 123, 135, 731, 1419 and 2779 differentially expressed genes (DEGs) at 10-min, 1-h, 6-h, 24-h and 72-h AMI, respectively, compared with the sham group. Remarkably, the 6-h AMI with the drastic changes of DEGs and a large number of enriched functional pathways in KEGG may be the most critical stage of AMI process. The 4, 9, 40, 26, and 183 genes were further identified at each time point, based on the negative correlation (P < 0.05) between the differential mRNA expression and the differential DNA methylation. The mRNA and the promoter methylation expressions of five genes (Ptpn6, Csf1r, Col6a1, Cyba, and Map3k14) were validated by qRT-PCR and BSP methods, and the mRNA expressions were further confirmed to be regulated by DNA methylation in cardiomyocytes in vitro. Conclusions Our findings profiled the molecular variations from the perspective of DNA methylation in the early stage of AMI and provided promising epigenetic-based biomarkers for the early clinical diagnosis and therapeutic targets of AMI.

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DNA methylation biomarkers of myocardial infarction and cardiovascular disease

Cited by 52 publications

References 41 publications

Diagnosis, clustering, and immune cell infiltration analysis of m6A-related genes in patients with acute myocardial infarction—a bioinformatics analysis

Diagnosis, clustering, and immune cell infiltration analysis of m6A-related genes in patients with acute myocardial infarction—a bioinformatics analysis

Targeting Epigenetics and Non-coding RNAs in Myocardial Infarction: From Mechanisms to Therapeutics

Integrative analysis of DNA methylation and gene expression reveals key molecular signatures in acute myocardial infarction

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