PO-02-143 RAP1 AND CAMP SIGNALING PATHWAY ARE ASSOCIATED WITH HIGHER BURDEN OF PREMATURE VENTRICULAR COMPLEX

Abstract

Higher burden of PVC is associated with heart failure and cardiovascular events. Genetic background and pathogenesis of premature ventricular complex (PVC) and PVC burden remain uncertain despite recent advances in mechanisms of arrhythmogenesis. To study the genetic background of higher burden of PVC in comparison with very low burden of PVC. A total of 1222 patients with both 24-hour Holter electrocardiogram data and genomic data were enrolled. Patients with very low daily burden PVC burden (<0.1%) were defined as group 1, and patients with moderate to high daily burden of PVC burden (>1%) were defined as group 2. Saliva samples were collected from enrolled patients for DNA extraction. Genotyping was performed according to the Infinium Asian Screening Array (ASA)-24 v1.0 BeadChip (Illumina, Inc., San Diego, CA, USA) and standard Illumina protocols. Propensity score matched (PSM) analysis is used to eliminate the clinical confounding factors between the two study groups. Gene enrichment analysis was performed by DAVID software to comprehensively observe the significant SNP involved in the pathways and GO terms. For functional annotation, significant KEGG pathways and GO terms were filtered by FDR < 0.05. After PSM analysis, 446 and 263 patients were enrolled within group 1 and group 2 respectively. A total of 280 single-nucleotide polymorphism (SNP) in 233 genes were found to be associated with higher burden of PVC. The pathway enrichment analysis showed that two signaling pathways, including cAMP (RYR2, PAK1, GABBR1, RAP1A, BAD, ARAP3, ADCY2, CACNA1C, GLI3, RHOA, SLC9A1, RAPGEF4; FDR=0.011) and Rap1 (ANGPT4, FLT1, RAP1A, FGF14, EGF, PDGFD, MAGI2, ARAP3, ADCY2, FGF12, RHOA, RAPGEF4; FDR=0.112) signaling axis, were associated with higher daily burden of PVC. cAMP and Rap1 signaling pathway are associated with higher daily burden of PVC.