Omics Data Integration Uncovers mRNA-miRNA Interaction Regions in Genes Associated with Chronic Venous Insufficiency

Area of Science:

• Genetics and Epigenetics
• Molecular Biology
• Vascular Biology

Background:

• Chronic venous insufficiency (CVI) is a prevalent vascular condition with significant health implications, including varicose veins and skin ulcers.
• Understanding the genetic and epigenetic underpinnings of CVI is crucial for improving patient outcomes.
• Previous genomic and transcriptomic studies have identified numerous CVI-associated genes, variants, and microRNAs (miRNAs).

Purpose of the Study:

• To investigate the role of common variants in mRNA-miRNA binding regions in CVI pathogenesis.
• To explore the regulatory mechanisms of CVI-associated genes by miRNAs.
• To identify specific miRNAs and genetic variants influencing CVI gene expression.

Main Methods:

• Utilized in silico analyses, including miRNA research tools, the miRNA binding site (MBS) database, and genome browsers.
• Employed the eQTL Calculator in the Genotype-Tissue Expression (GTEx) portal for variant analysis.
• Examined single nucleotide variants (SNVs) in mRNA-miRNA binding sites of CVI-related genes and miRNAs.

Main Results:

• Identified SNVs potentially involved in miRNA-mediated regulation of key CVI genes: ZNF664, COL1A2, HFE, MDN, MTHFR, SRPX, TDRD5, TSPYL4, VEGFA, and APOE.
• Discovered seven miRNAs associated with the expression profiles of ABCA1, PIEZO1, and CASZ1 genes through analysis of common SNVs in mRNA binding regions.
• Established a link between genetic markers, CVI pathogenesis, and gene expression profiles within the mRNA-miRNA interaction axis.

Conclusions:

• This study provides novel insights into the mRNA-miRNA interaction axis in CVI pathogenesis.
• The findings highlight specific genetic variants and miRNAs that may serve as potential biomarkers or therapeutic targets for CVI.
• This research represents a first-time evaluation of the relationship between identified genetic markers and gene expression profiles in the context of mRNA-miRNA interactions in CVI.