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Article Dans Une Revue Journal of the American Heart Association Année : 2023

Impact of Neuroeffector Adrenergic Receptor Polymorphisms on Incident Ventricular Fibrillation During Acute Myocardial Ischemia

Facteurs prédictifs de grossesse spontanée chez les chez les femmes présentant une réserve ovarienne diminuée traitées par DHEA

Philippe Chevalier
Francis Bessière
Elodie Morel
Bénédicte Ankou
  • Fonction : Auteur
Gina Morgan
Indrani Halder
  • Fonction : Auteur
Barry London
Wayne Minobe
Dobromir Slavov
  • Fonction : Auteur
Antoine Delinière
Thomas Bochaton
Franck Paganelli
Nathalie Lesavre
  • Fonction : Auteur
Clément Boiteux
Jacques Mansourati
Philippe Maury
Gaël Clerici
Pierre François Winum
  • Fonction : Auteur
Sophia Huebler
  • Fonction : Auteur
Ian Carroll
Michael Bristow

Résumé

Background Cardiac adrenergic receptor gene polymorphisms have the potential to influence risk of developing ventricular fibrillation (VF) during ST‐segment‐elevation myocardial infarction, but no previous study has comprehensively investigated those most likely to alter norepinephrine release, signal transduction, or biased signaling. Methods and Results In a case–control study, we recruited 953 patients with ST‐segment‐elevation myocardial infarction without previous cardiac history, 477 with primary VF, and 476 controls without VF, and genotyped them for ADRB1 Arg389Gly and Ser49Gly, ADRB2 Gln27Glu and Gly16Arg, and ADRA2C Ins322‐325Del. Within each minor allele‐containing genotype, haplotype, or 2‐genotype combination, patients with incident VF were compared with non‐VF controls by odds ratios (OR) of variant frequencies referenced against major allele homozygotes. Of 156 investigated genetic constructs, 19 (12.2%) exhibited significantly ( P <0.05) reduced association with incident VF, and none was associated with increased VF risk except for ADRB1 Gly389 homozygotes in the subset of patients not receiving β‐blockers. ADRB1 Gly49 carriers (prevalence 23.0%) had an OR (95% CI) of 0.70 (0.49–0.98), and the ADRA2C 322–325 deletion (Del) carriers (prevalence 13.5%) had an OR of 0.61 (0.39–0.94). When present in genotype combinations (8 each), both ADRB1 Gly49 carriers (OR, 0.67 [0.56–0.80]) and ADRA2C Del carriers (OR, 0.57 [0.45– 0.71]) were associated with reduced VF risk. Conclusions In ST‐segment‐elevation myocardial infarction, the adrenergic receptor minor alleles ADRB1 Gly49, whose encoded receptor undergoes enhanced agonist‐mediated internalization and β‐arrestin interactions leading to cardioprotective biased signaling, and ADRA2C Del322‐325, whose receptor causes disinhibition of norepinephrine release, are associated with a lower incidence of VF. Registration URL: https://clinicaltrials.gov ; Unique identifier: NCT00859300.

Dates et versions

hal-04152335 , version 1 (05-07-2023)

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Citer

Philippe Chevalier, Pascal Roy, Francis Bessière, Elodie Morel, Bénédicte Ankou, et al.. Impact of Neuroeffector Adrenergic Receptor Polymorphisms on Incident Ventricular Fibrillation During Acute Myocardial Ischemia. Journal of the American Heart Association, 2023, 12 (6), ⟨10.1161/JAHA.122.025368⟩. ⟨hal-04152335⟩

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