Evidence mapPaperPMID 38849833Full record

ArticleCardiovascular diabetology2024

Dysregulation of long non-coding RNA gene expression pathways in monocytes of type 2 diabetes patients with cardiovascular disease.

Najeeb Halabi, Binitha Thomas, Omar Chidiac, Amal Robay, Julien AbiNahed, Amin Jayyousi, Jassim Al Suwaidi, Martina Bradic, Charbel Abi Khalil

Abstract read
In one paragraph

Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Najeeb HalabiEpigenetics Cardiovascular Lab, Department of Genetic Medicine, Weill Cornell Medicine - Qatar, PO box 24144, Doha, Qatar.
Binitha ThomasEpigenetics Cardiovascular Lab, Department of Genetic Medicine, Weill Cornell Medicine - Qatar, PO box 24144, Doha, Qatar.
Omar ChidiacEpigenetics Cardiovascular Lab, Department of Genetic Medicine, Weill Cornell Medicine - Qatar, PO box 24144, Doha, Qatar.
Amal RobayEpigenetics Cardiovascular Lab, Department of Genetic Medicine, Weill Cornell Medicine - Qatar, PO box 24144, Doha, Qatar.
Julien AbiNahedTechnology Innovation Unit, Hamad Medical Corporation, Doha, Qatar.
Amin JayyousiDepartment of Endocrinology, Hamad Medical Corporation, Doha, Qatar.
Jassim Al SuwaidiHeart Hospital, Hamad Medical Corporation, Doha, Qatar.
Martina BradicDepartment of Genetic Medicine, Weill Cornell Medicine, New York, USA.
Charbel Abi KhalilEpigenetics Cardiovascular Lab, Department of Genetic Medicine, Weill Cornell Medicine - Qatar, PO box 24144, Doha, Qatar. cha2022@med.cornell.edu.ORCID 0000-0002-1428-6324

Funding

The Patient-Reported Outcomes, Community-Engagement and Language (PRO-CEL) CoreP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · 1985 to 2025
$88.4M
NCI NIH HHS P30 CA008748Qatar Foundation Biomedical Research Program (BMRP) at Weill Cornell Medicine- Qatar
6 · The paper itself

Abstract

backgroundMonocytes play a central role in the pathophysiology of cardiovascular complications in type 2 diabetes (T2D) patients through different mechanisms. We investigated diabetes-induced changes in lncRNA genes from T2D patients with cardiovascular disease (CVD), long-duration diabetes, and poor glycemic control.

methodsWe performed paired-end RNA sequencing of monocytes from 37 non-diabetes controls and 120 patients with T2D, of whom 86 had either macro or microvascular disease or both. Monocytes were sorted from peripheral blood using flow cytometry; their RNA was purified and sequenced. Alignments and gene counts were obtained with STAR to reference GRCh38 using Gencode (v41) annotations followed by batch correction with CombatSeq. Differential expression analysis was performed with EdgeR and pathway analysis with IPA software focusing on differentially expressed genes (DEGs) with a p-value < 0.05. Additionally, differential co-expression analysis was done with csdR to identify lncRNAs highly associated with diabetes-related expression networks with network centrality scores computed with Igraph and network visualization with Cytoscape.

resultsComparing T2D vs. non-T2D, we found two significantly upregulated lncRNAs (ENSG00000287255, FDR = 0.017 and ENSG00000289424, FDR = 0.048) and one significantly downregulated lncRNA (ENSG00000276603, FDR = 0.017). Pathway analysis on DEGs revealed networks affecting cellular movement, growth, and development. Co-expression analysis revealed ENSG00000225822 (UBXN7-AS1) as the highest-scoring diabetes network-associated lncRNA. Analysis within T2D patients and CVD revealed one lncRNA upregulated in monocytes from patients with microvascular disease without clinically documented macrovascular disease. (ENSG00000261654, FDR = 0.046). Pathway analysis revealed DEGs involved in networks affecting metabolic and cardiovascular pathologies. Co-expression analysis identified lncRNAs strongly associated with diabetes networks, including ENSG0000028654, ENSG00000261326 (LINC01355), ENSG00000260135 (MMP2-AS1), ENSG00000262097, and ENSG00000241560 (ZBTB20-AS1) when we combined the results from all patients with CVD. Similarly, we identified from co-expression analysis of diabetes patients with a duration ≥ 10 years vs. <10 years two lncRNAs: ENSG00000269019 (HOMER3-AS10) and ENSG00000212719 (LINC02693). The comparison of patients with good vs. poor glycemic control also identified two lncRNAs: ENSG00000245164 (LINC00861) and ENSG00000286313.

conclusionWe identified dysregulated diabetes-related genes and pathways in monocytes of diabetes patients with cardiovascular complications, including lncRNA genes of unknown function strongly associated with networks of known diabetes genes.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Gene Expression ProfilingGene Expression RegulationGene Regulatory NetworksMonocytesRNA, Long NoncodingAgedBlood GlucoseCase-Control StudiesFemaleHumansMaleMiddle AgedRNA-SeqSignal TransductionBlood GlucoseRNA, Long NoncodingCardiovascular diseaseLong non-coding RNAsMacrovascular diseaseMicrovascular diseaseType 2 diabetes

Identifiers

PMID38849833
PMCPMC11161966

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.