[Retracted] Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy

Abstract

Objective. Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. Methods. Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. Results. 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 ( degree = 24 ), GNB3 ( degree = 23 ), QSOX1 ( degree = 21 ), and APOB ( degree = 17 ). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. Conclusion. Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.

Lamin A K97E leads to NF‐κB‐mediated dysfunction of inflammatory responses in dilated cardiomyopathy

“…In addition, cytokine–cytokine receptor interaction and chemokine‐mediated signaling pathways were differentially regulated. Intriguingly, this is consistent with the previous DCM‐associated transcriptome studies (Liu et al., 2021; Zhang et al., 2021). However, genes from the most strongly affected signaling pathways (IL‐17 signaling and cytokine production) were downregulated in the mutant, whereas most clinical investigations have reported elevated cytokine levels in cardiomyopathy patients (Gerbino et al., 2021).…”

Integrative bioinformatics analysis of potential therapeutic targets and immune infiltration characteristics in dilated cardiomyopathy

“…In addition, ASPN has been found to increase significantly in DCM left ventricle samples (27), while the PHLDA1 gene mutation is differentially expressed in DCM and control groups (28). In 1 study, the conditional mutant IDH2 mice exhibited DCM, characterized by severely reduced wall motion and increased dilatation (29).…”

AHNAKs roles in physiology and malignant tumors

“…In contrast, decreased expression of AHNAK2 was detected after ANRIL knockdown ( 15 ). In patients with atrial fibrillation (AF) and dilated cardiomyopathy, AHNAK2 was one of the three most frequently mutated genes, with respective mutation rates of 52% and 51% ( 16 , 17 ). These results suggest that AHNAK2 may participate in the regulation of heart disease, although the specific molecular mechanism is not clear.…”