Journal article
A Genotype-Phenotype Analysis of Glutathione Peroxidase 4 in Human Atrial Myocardium and Its Association with Postoperative Atrial Fibrillation
Antioxidants, Vol.11(4), p.721
04/06/2022
DOI: 10.3390/antiox11040721
PMCID: PMC9026099
PMID: 35453406
Abstract
Heterogeneity in the incidence of postoperative atrial fibrillation (POAF) following heart surgery implies that underlying genetic and/or physiological factors impart a higher risk of this complication to certain patients. Glutathione peroxidase-4 (GPx4) is a vital selenoenzyme responsible for neutralizing lipid peroxides, mediators of oxidative stress known to contribute to postoperative arrhythmogenesis. Here, we sought to determine whether
single nucleotide variants are associated with POAF, and whether any of these variants are linked with altered
enzyme content or activity in myocardial tissue. Sequencing analysis was performed across the
coding region within chromosome 19 from a cohort of patients (N = 189) undergoing elective coronary artery bypass graft (-/+ valve) surgery. GPx4 enzyme content and activity were also analyzed in matching samples of atrial myocardium from these patients. Incidence of POAF was 25% in this cohort. Five
variants were associated with POAF risk (permutated
≤ 0.05), and eight variants associated with altered myocardial GPx4 content and activity (
< 0.05). One of these variants (rs713041) is a well-known modifier of cardiovascular disease risk. Collectively, these findings suggest
variants are potential risk modifiers and/or predictors of POAF. Moreover, they illustrate a genotype-phenotype link with this selenoenzyme, which will inform future mechanistic studies.
Details
- Title: Subtitle
- A Genotype-Phenotype Analysis of Glutathione Peroxidase 4 in Human Atrial Myocardium and Its Association with Postoperative Atrial Fibrillation
- Creators
- Islam A Berdaweel - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USAAlexander A Hart - University of IowaAndrew J Jatis - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USANathan Karlan - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USAShahab A Akhter - Heart InstituteMarie E Gaine - University of IowaRyan M Smith - University of IowaEthan J Anderson - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Antioxidants, Vol.11(4), p.721
- DOI
- 10.3390/antiox11040721
- PMID
- 35453406
- PMCID
- PMC9026099
- NLM abbreviation
- Antioxidants (Basel)
- ISSN
- 2076-3921
- eISSN
- 2076-3921
- Grant note
- R01HL122863 / NIH HHS R21AG057006 / NIH HHS 20SFRN35200003 / American Heart Association W81XWH-19-1-0037 / Congressionally Directed Medical Research Programs
- Language
- English
- Date published
- 04/06/2022
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984251446002771
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