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Gene signatures of postoperative atrial fibrillation in atrial tissue after coronary artery bypass grafting surgery in patients receiving β-blockers
- Publication Year :
- 2016
-
Abstract
- Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to β-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate < 0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate < 0.25. The most significant probe corresponded to vesicular overexpressed in cancer – prosurvival protein 1 gene (VOPP1; 1.83 fold change; P = 3.47 × 10−7), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P = 1.54 × 10−5), was down-regulated in patients with postoperative AF. GSEA highlighted the role of VOPP1 in pathways with biologic relevance to myocardial homeostasis, and oxidative stress and redox modulation. Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. In patients undergoing CABG surgery, RAA gene expression profiling, and pathway and eQTL analysis suggested that VOPP1 plays a novel etiological role in postoperative AF despite perioperative BB therapy.
- Subjects :
- 0301 basic medicine
G-Protein-Coupled Receptor Kinase 5
Male
Candidate gene
medicine.medical_specialty
Genotype
Adrenergic beta-Antagonists
Single-nucleotide polymorphism
030204 cardiovascular system & hematology
Biology
Bioinformatics
Polymorphism, Single Nucleotide
Article
03 medical and health sciences
0302 clinical medicine
Gene expression
Atrial Fibrillation
medicine
Humans
Heart Atria
Postoperative Period
Coronary Artery Bypass
Molecular Biology
Aged
Myocardium
Atrial fibrillation
Perioperative
Middle Aged
medicine.disease
Fold change
Surgery
Gene expression profiling
Oxidative Stress
030104 developmental biology
Gene Expression Regulation
Expression quantitative trait loci
Female
Cardiology and Cardiovascular Medicine
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....6609e50076689051586cd8348bfff753