Genetic/ Epigenetic RNA dysregulation in Type 2 Diabetes mellitus complicated with ischemic heart disease

Eslam Saadawy Sedkey^1*Marwa Matboli Sayed²Mohamed Gomaa Seadawy³Marwa Galal Eldeen Hegazy^1*

• ¹Biochemistry department, Faculty of Science, Ain Shams University., Cairo, Egypt
• ²Medical Biochemistry and Molecular Biology department, Faculty of Medicine, Ain Shams University., Cairo, Egypt
• ³Biological Prevention department, Ministry of Defense, Egypt., Cairo, Egypt

Introduction: 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. Methods: 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. Results: 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. Discussion: 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.