TERT and TET2 Genetic Variants Affect Leukocyte Telomere Length and Clinical Outcome in Coronary Artery Disease Patients—A Possible Link to Clonal Hematopoiesis

Opstad, Trine Baur; Solheim, Svein; Pettersen, Alf-Åge R.; Kalstad, Are Annesønn; Arnesen, Harald; Seljeflot, Ingebjørg

doi:10.3390/biomedicines10082027

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…Recent studies have shown that altered expression of DDX58 [413], STAT1 [414], TLR4 [415], CYP2D6 [416], JAK2 [417], TLR2 [418], DUSP6 [419], HDAC9 [420], LATS2 [421], CA2 [150], HIPK3 [422], CCR2 [423], GAB1 [120], UFL1 [424], OGT (O-linked N-acetylglucosamine (GlcNAc) transferase) [425], PRKAR1A [265], SIRT1 [426], FGL2 [427], TET2 [428], ASCC2 [429], BIN1 [430], HSPB1 [431], IGFBP4 [432], TRPM4 [433] and LGALS3 [434] might be associated with the progression of heart failure. STAT1 [435], TLR4 [436], ABCA1 [437], PTGS2 [68], CYP2D6 [438], CR1 [439], PDK4 [440], RNF213 [441], ZDHHC17 [70], TLR8 [442], PDGFC (platelet derived growth factor C) [443], TLR2 [444], CYP1B1 [445], HDAC9 [446], IL1RN [447], GCH1 [448], EGR1 [449], ZEB2 [450], PLA2G7 [451], CCR2 [452], GCLC (glutamate-cysteine ligase catalytic subunit) [258], VEGFA (vascular endothelial growth factor A) [453], CD46 [454], NFKBIZ (NFKB inhibitor zeta) [455], LDLR (low density lipoprotein receptor) [456], TLR6 [457], SIRT1 [458], NOD2 [459], FGL2 [460], IDH1 [461], TET2 [462], PFKFB2 [463], KDM6A [464], IKZF2 [465], ZNF606 [466], PF4 [467], CCR7 [468], RUNX3 [469], TCF7 [470], PPBP (pro-platelet basic protein) [471], IGFBP4 [280], HSPG2 [472] and LGALS3 [236] expression might be regarded as an indicator of susceptibility to CAD. STAT1 [473], TLR4 [367], JAK2 [474], PDGFC (platelet derived growth factor C) […”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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Coronary artery disease (CAD) is the most common cardiovascular disorder and the leading cause of heart related deaths in world. Increasing molecular targets have been discovered for CAD and CAD - related complications prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might help the diagnosis and treatment of CAD and CAD related complications. We searched next generation sequencing (NGS) dataset (GSE202625) and identified differentially expressed genes (DEGs) by comparing CAD and normal control samples using DESeq2. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g:Profiler online database. The protein protein interaction (PPI) network was plotted with IMEx interactome and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. MiRNA hub gene regulatory network and TF hub gene regulatory network analysis was performed to identify the hub genes, miRNAs and TFs. Receiver operating characteristic (ROC) curve analysis was used to predict the diagnostic effectiveness of the hub genes. A total of 118 DEGs (479 up regulated genes and 479 down regulated genes) were detected. The GO enrichment analysis indicated that the DEGs most significantly enriched in cellular response to stimulus and biosynthetic process. The REACTOME pathway enrichment analysis revealed that the DEGs were most significantly enriched in immune system and eukaryotic translation elongation. PPI network, modules, miRNA hub gene regulatory network and TF hub gene regulatory network analysis demonstrated that EGR1, SIRT1, STAT1, LRRK2, HIF1A, CSNK2B, RPS3, RPS2, RPS4X and HDAC11 were the hub genes. On the whole, the findings of this study enhance our understanding of the potential molecular mechanisms of CAD and CAD-related complications, and provide potential targets for further research.

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Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Vastrad¹,

Vastrad²

2023

Preprint

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“…As this enzyme effectively reduces telomere length, several commentators have suggested it may be a new therapeutic target (16,17). Over-expression of human TERT (h-TERT), coded for by TERT at 5p15.33, may be important in cancer (18), whilst variants of TERT may be linked to outcome in stable CAD (19) and risk of ischaemic stroke (20).…”

Section: Introductionmentioning

confidence: 99%

A pilot study of increased gene expression of Growth Differentiation Factor 15 and Telomerase Reverse Transcriptase in the middle-aged with acute coronary artery disease

Abdelsabour,

Idriss,

Blann

et al. 2023

Preprint

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Introduction: Growth Differentiation Factor 15 (GDF15) and Telomerase Reverse Transcriptase (TERT) may have roles as serum biomarkers of the pathophysiology of cardiovascular disease. We hypothesised altered genomic expression of the genes for these molecules in middle aged subjects with acute coronary artery disease. Method: Venous blood was obtained from 53 patients (27 with diabetes) presenting with an acute coronary syndrome and subsequently shown to have coronary artery disease (CAD), and from 46 age and sex matched controls free of cardiovascular disease and its risk factors. Relative expression of leukocyte transcriptome GAPDH, GDF15and TERT were determined by RT-PCR and quantified by quantitation-comparative Ct (ΔΔCt). Results: Compared to expression in controls, mean (95% confidence interval) relative expression of GDF15in the patients was 1.38 (1.13-1.49) (p<0.001), and of TERT was 1.12 (1.04-1.20) p=0.003), with relative expression of GDF15 being greater than that of TERT (p<0.001). Expression of the two genes failed to correlate significantly in the controls (r=0.22, p=0.131) but did so in the patients (r=0.55, p<0.01). There was no difference in relative expression of GDF15 in 26 patients free of diabetes (1.6 [1.42-1.78]) compared to those 27 with diabetes (1.6 [1.29-1.91]) (p=0.996). Similarly, there was no difference in the expression of TERT in patients free of diabetes (1.19 [1.06-1.33]) compared to those with diabetes (1.25 [0.98-1.50]) (p=0.739). Conclusion: Relative expression of GDF15 and TERTare both increased in middle-aged patients with CAD and in CAD+diabetes, with no difference between the patient groups. These genes may have roles in the pathogenesis of acute coronary artery disease.

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“…Telomere shortening is associated with obesity, 10 diabetes, 11 and metabolic syndrome. 12 Studies have also shown that shortened telomere length is a risk factor for cardiovascular disease. 13 Coal miners are exposed to PAHs and other toxic substances for a longer time than the general population due to the unique aspects of their profession and working surroundings.…”

mentioning

confidence: 99%

“…Telomeres are DNA-protein complexes located at the ends of chromosomes that protect the integrity of chromosomes and control the mitotic cycle of cells. Telomere shortening is associated with obesity, 10 diabetes, 11 and metabolic syndrome 12 . Studies have also shown that shortened telomere length is a risk factor for cardiovascular disease 13 …”

mentioning

confidence: 99%

Effects of Polycyclic Aromatic Hydrocarbon Exposure and Telomere Length and their Interaction on Blood Lipids in Coal Miners

Wang,

Chang,

Zhang

et al. 2023

J Occup Environ Med

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Objective This study aimed to investigate the effects of PAH exposure and telomere length on lipids in coal miners. Methods Basic personal information of 637 coal miners was collected by questionnaire survey. Logistic regression, the Bayesian kernel machine regression (BKMR) model, and weighted quantile sum (WQS) regression were used to analyze the effects of PAH metabolites and telomere length and their interactions on blood lipids. Results High exposure to 9-hydroxyphenanthrene (OR = 1.586, 95% CI: 1.011-2.487) and telomere shortening (OR = 1.413, 95% CI: 1.005-1.985) were associated with dyslipidemia. WQS results showed that 9-hydroxyphenanthrene accounted for the largest proportion of dyslipidemia (weight = 0.66). The interaction results showed that high 9-hydroxyphenanthrene exposure and short telomeres were risk factors for dyslipidemia in coal miners (OR = 2.085, 95% CI: 1.121-3.879). Conclusion Our findings suggest that 9-hydroxyphenanthrene and shorter telomeres are risk factors for dyslipidemia, and their interaction increases the risk of dyslipidemia.

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TERT and TET2 Genetic Variants Affect Leukocyte Telomere Length and Clinical Outcome in Coronary Artery Disease Patients—A Possible Link to Clonal Hematopoiesis

Cited by 7 publications

References 31 publications

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

A pilot study of increased gene expression of Growth Differentiation Factor 15 and Telomerase Reverse Transcriptase in the middle-aged with acute coronary artery disease

Effects of Polycyclic Aromatic Hydrocarbon Exposure and Telomere Length and their Interaction on Blood Lipids in Coal Miners

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