Effect of Clinical and Genetic Factors on the Development of Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting (CABG) in Egyptian Patients Receiving Beta-Blockers

Abstract

Purpose Prophylactic beta-blockers are recommended to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). Polymorphisms in the beta-1 adrenergic receptor (ADRB1) and G protein-coupled receptor kinase 5 (GRK5) genes are associated with variable responses to beta-blockers. The aim of this study was to determine the clinical and genetic factors that influence the response to beta-blockers for POAF prophylaxis after CABG. Methods Patients undergoing isolated CABG and receiving prophylactic beta-blockers (n = 249) were prospectively recruited and followed up for 6 postoperative days. Genotyping of ADRB1 rs1801253, and 3 GRK5 SNPs (rs3740563, rs10787959, and rs17098707) was performed. Results Of the 249 patients, 52 patients (20.8%) experienced POAF. Age, hypertension, vasopressor use, calculated POAF risk score, GRK5 rs2230345 T-allele, and GRK5 rs3740563 A-allele were associated with POAF despite beta-blocker prophylaxis. The multivariate analysis revealed that age [odds ratio (OR) 1.06, 95% CI 1.02–1.11, p = 0.003] and GRK5 rs2230345 T-allele [OR 2.81, 95% CI 1.39–5.67, p = 0.004] were independent predictors of POAF after CABG despite beta-blocker prophylaxis. Conclusion GRK5 rs2230345 T-allele carriers were less responsive than AA genotype carriers to prophylactic beta-blockers for the prevention of POAF after CABG. The study was registered on http://clinicaltrials.gov in March 2019, with trial registration number (TRN): NCT03871647.

β1-Adrenergic Receptor Polymorphisms: A Possible Genetic Predictor of Bisoprolol Response in Acute Coronary Syndrome

“…The frequency of the rs1801252 Gly-allele (Ser49Gly polymorphism) in our study was found to be 14% which is close to the frequency of Europeans (13%), similar to East Asians (14%) but lower than Africans (24%), importantly, this's the first study to provide data on allelic frequency for Ser49Gly polymorphism in the Egyptian population. On the other hand, the frequency of the rs1801253 Gly-allele (Arg389Gly) was found to be 36% which is in good alignment with the findings of recent pharmacogenetic study in Egyptians (40%) [ 29 ], to some degree different from Africans (42%) and Europeans (32%) but higher than East Asians (21%). The discrepancy in the MAF of the studied SNPs between Egyptians and other populations implies a potential admixed genetic makeup among Egyptians.…”

“…The rs1801252 Gly-allele frequency was similar to Europeans, East Asians and the global population, but lower than Africans. The rs1801253 Gly-allele frequency was closer to Africans and a recent pharmacogenetic study in Egyptians [ 29 ] but higher than Europeans, Asians and global population.…”

“…Allele frequencies obtained from the 1000 Genome, Phase III data [ 28 ]. Egyptian study, El Gindy et al 2022 [ 29 ].…”

Predictive factors of atrial fibrillation after coronary bypass surgery in a comparative Latin American cohort.

“…The results obtained are comparable with the data of surgical risk scores, including EuroSCORE II, STS and Logistic Euroscore, for their predictive capacity in relation to FAPO, it was observed that according to the results of the ROC analysis, the AUC was higher for EuroSCORE II (AUC = 0.69) than according to the STS and Logistic Euroscore scales (0.65 and 0.65, respectively) [10,11].…”