title: Genetic variation in alpha2-adrenoreceptors and heart rate recovery after exercise.
abstract: Heart rate recovery (HRR) after exercise is an independent predictor of adverse cardiovascular outcomes. HRR is mediated by both parasympathetic reactivation and sympathetic withdrawal and is highly heritable. We examined whether common genetic variants in adrenergic and cholinergic receptors and transporters affect HRR. In our study 126 healthy subjects (66 Caucasians, 56 African Americans) performed an 8 min step-wise bicycle exercise test with continuous computerized ECG recordings. We fitted an exponential curve to the postexercise R-R intervals for each subject to calculate the recovery constant (kr) as primary outcome. Secondary outcome was the root mean square residuals averaged over 1 min (RMS1min), a marker of parasympathetic tone. We used multiple linear regressions to determine the effect of functional candidate genetic variants in autonomic pathways (6 ADRA2A, 1 ADRA2B, 4 ADRA2C, 2 ADRB1, 3 ADRB2, 2 NET, 2 CHT, and 1 GRK5) on the outcomes before and after adjustment for potential confounders. Recovery constant was lower (indicating slower HRR) in ADRA2B 301-303 deletion carriers (n = 54, P = 0.01), explaining 3.6% of the interindividual variability in HRR. ADRA2A Asn251Lys, ADRA2C rs13118771, and ADRB1 Ser49Gly genotypes were associated with RMS1min. Genetic variability in adrenergic receptors may be associated with HRR after exercise. However, most of the interindividual variability in HRR remained unexplained by the variants examined. Noncandidate gene-driven approaches to study genetic contributions to HRR in larger cohorts will be of interest.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee;
authors.forename: Utkarsh
authors.initials: U
authors.lastname: Kohli
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Biomedical Engineering Vanderbilt University, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee;
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.affiliation: Department of Pediatrics, Vanderbilt University, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee;
authors.forename: Prince J
authors.initials: PJ
authors.lastname: Kannankeril
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee;
authors.forename: Mordechai
authors.initials: M
authors.lastname: Muszkat
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee;
authors.forename: Gbenga G
authors.initials: GG
authors.lastname: Sofowora
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Division of Genetic Medicine, Vanderbilt University, Nashville, Tennessee; and Centre for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee;
authors.forename: Maureen K
authors.initials: MK
authors.lastname: Hahn
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Parexel International Early Phase, Glendale, California; and.
authors.forename: Brett A
authors.initials: BA
authors.lastname: English
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Department of Psychiatry, Vanderbilt University, Nashville, Tennessee; Centre for Molecular Neuroscience, Vanderbilt University, Nashville, Tennessee;
authors.forename: Randy D
authors.initials: RD
authors.lastname: Blakely
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee;
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, Tennessee; Department of Pharmacology, Vanderbilt University, Nashville, Tennessee; Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee; Clinical Pharmacology Unit, Section of Clinical Pharmacology and Toxicology, Rambam Health Care Campus, Haifa, Israel daniel.kurnik@vanderbilt.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kurnik
mesh_terms: D000328:Adult; D002395:Catecholamines / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016014:Linear Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics
chemical_list: C547768:ADRA2A protein, human; C547771:ADRA2B protein, human; C547774:ADRA2C protein, human; C547787:ADRB1 protein, human; D002395:Catecholamines; D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1
keywords: adrenergic; cholinergic; heart rate recovery; parasympathetic tone; polymorphisms