Genetic/epigenetic RNA dysregulation in type 2 diabetes mellitus complicated with ischemic heart disease

TL;DR

This study identifies a panel of RNA biomarkers that can help detect and distinguish ischemic heart disease in people with type 2 diabetes.

Contribution

The study introduces a novel RNA panel for early detection of ischemic heart disease in type 2 diabetes patients.

Findings

The RNA panel showed high discriminatory performance (AUC = 0.94) between T2DM+IHD and controls.

hsa-miR-1976, FZD5, and GTF2I were upregulated, while LINC02210 was downregulated in T2DM+IHD patients.

The RNA panel includes both mRNAs and non-coding RNAs linked to angiogenesis and disease pathways.

Abstract

Diabetes mellitus is a major independent determinant of cardiovascular morbidity. Therefore, we evaluated whether a molecular RNA panel comprising FZD5 and GTF2I could facilitate the early detection and discrimination of ischemic heart disease in individuals with type 2 diabetes mellitus.

We implemented a two-stage bioinformatics workflow to identify and validate two mRNA candidates associated with T2DM and IHD. Subsequently, we delineated non-coding RNAs linked to these transcripts and the pathways potentially implicated in T2DM complicated by IHD. Finally, we conducted a pilot case–control study and quantified the panel members by RT-qPCR in 56 patients with T2DM, 25 with IHD, 26 with combined T2DM+IHD, and 60 matched controls.

Differential expression analysis showed upregulation of hsa-miR-1976, FZD5, and GTF2I, accompanied by downregulation of LINC02210 in the T2DM+IHD group versus controls. The RNA panel achieved high discriminatory performance (AUC = 0.94) between T2DM+IHD and controls, highlighting its potential as a discriminatory tool.

this study identified clinically relevant non-coding RNA–based angiogenesis panel (FZD5, GTF2I mRNAs, hsa-miR-1976 and LINC02210 lncRNA) as a biomarker signature associated with type 2 diabetes mellitus complicated by ischemic heart disease.

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