Integrative Genomic Profiling Reveals Novel Diagnostic Signatures in Congenital Heart Disease with Pulmonary Arterial Hypertension

Abstract

High pressure in the lung arteries that keeps getting worse is called pulmonary arterial hypertension (PAH). Children with congenital heart disease (CHD) are commonly affected. PAH-CHD accounts for approximately 28% of all PAH cases, significantly impacting patients’ quality of life. Exact mechanism still unclear. Studies point to cellular and molecular factors, genetic changes among them. This study sought genetic variants tied to PAH-CHD occurrence, using a genetic-driven biomarker approach. A bioinformatic-based method was employed, integrating multiple genomic databases. Data were drawn from several resources, including the Genome-Wide Association Studies (GWAS) catalog, GTEx portal, HaploReg version 4.1, and Ensembl databases. The aim was to explore genes that heighten vulnerability to PAH-CHD. Using integrated bioinformatics analysis, several key genes were identified as potentially involved in the pathogenesis of PAH-CHD. Notably, HLA-DPA1, BMPR2, TBX4, and SOX17 emerged as candidate genes that may contribute to disease susceptibility. These genes have been previously implicated in vascular and cardiac developmental pathways, supporting their possible roles in PAH-CHD. This study demonstrates the utility of a bioinformatics-driven approach to uncover genetic variants potentially involved in PAH-CHD. The identified genes may serve as valuable biomarkers, offering insights into disease mechanisms and potential targets for further investigation and therapeutic development.