Frontiers in Endocrinology (Apr 2024)

Transcriptional profiles associated with coronary artery disease in type 2 diabetes mellitus

  • Jose B. Nevado,
  • Eva Maria C. Cutiongco-de la Paz,
  • Eva Maria C. Cutiongco-de la Paz,
  • Elizabeth T. Paz-Pacheco,
  • Gabriel V. Jasul,
  • Aimee Yvonne Criselle L. Aman,
  • Christian Deo T. Deguit,
  • Jana Victoria B. San Pedro,
  • Mark David G. Francisco

DOI
https://doi.org/10.3389/fendo.2024.1323168
Journal volume & issue
Vol. 15

Abstract

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BackgroundCoronary artery disease (CAD) is a common complication of Type 2 diabetes mellitus (T2DM). Understanding the pathogenesis of this complication is essential in both diagnosis and management. Thus, this study aimed to characterize the presence of CAD in T2DM using molecular markers and pathway analyses.MethodsThe study is a sex- and age-frequency matched case-control design comparing 23 unrelated adult Filipinos with T2DM-CAD to 23 controls (DM with CAD). Healthy controls served as a reference. Total RNA from peripheral blood mononuclear cells (PBMCs) underwent whole transcriptomic profiling using the Illumina HumanHT-12 v4.0 expression beadchip. Differential gene expression with gene ontogeny analyses was performed, with supporting correlational analyses using weighted correlation network analysis (WGCNA).ResultsThe study observed that 458 genes were differentially expressed between T2DM with and without CAD (FDR<0.05). The 5 top genes the transcription factor 3 (TCF3), allograft inflammatory factor 1 (AIF1), nuclear factor, interleukin 3 regulated (NFIL3), paired immunoglobulin-like type 2 receptor alpha (PILRA), and cytoskeleton-associated protein 4 (CKAP4) with AUCs >89%. Pathway analyses show differences in innate immunity activity, which centers on the myelocytic (neutrophilic/monocytic) theme. SNP-module analyses point to a possible causal dysfunction in innate immunity that triggers the CAD injury in T2DM.ConclusionThe study findings indicate the involvement of innate immunity in the development of T2DM-CAD, and potential immunity markers can reflect the occurrence of this injury. Further studies can verify the mechanistic hypothesis and use of the markers.

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