PO-02-146 MULTI-OMICS ANALYSIS REVEALS THE METABOLIC AND POLYGENIC BASIS OF BRUGADA SYNDROME

Brugada syndrome (BrS) is an inherited disorder that can lead to sudden cardiac death. Candidate genes primarily include those encoding the sodium channel, whereas other genetic variants affecting channels, signaling, scaffold, sarcomere, and mitochondrial proteins are controversial, leaving architecture of BrS largely unknown. The aim this work was improve diagnosis prognosis BrS, further understanding its molecular basis by performing first study integrates genetics, transcriptomics, proteomics, metabolomics, lipidomics in patients with without BrS. Transcriptomics, lipidomics, whole-genome sequencing analyzes were performed on PBMCs plasma samples 293 295 control patients. These datasets integrated provide a comprehensive view pathways factors underlying WGS showed polygenic contribute there overlap arrhythmogenic, cardiovascular, noncardiac pathologies. This complex background includes pathogenic mutations SCN5A such as CACNB2, MUC4, CHIT1, MME, PFKFB3, ACSF3, ACACB, SLC27A6, PLCG2, MT-CYB. Many them regulate metabolic functions related lipid metabolism energy production. Transcriptomics proteomics analyses independently confirmed dysregulation signaling pathways, indicative chronic oxidative abnormalities. reflected changes metabolomics including downregulation TCA cycle, decreased ATP production, evidence shift from phosphorylation glycolysis. Integration multi-omics analysis patients' peripheral blood cells revealed ubiquitous revealing not limited heart. challenges traditional classification channelopathy suggests possible role disease pathophysiology.