Document Detail


β-1 and β-2 adrenergic receptor polymorphism and association with cardiovascular response to orthostatic screening.
MedLine Citation:
PMID:  21807569     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Variation in the beta-1 and beta-2 adrenergic receptor genes (ADRB1 and ADRB2, respectively) may influence cardiovascular reactivity including orthostatic stress. We tested this hypothesis in a head-up tilt (HUT) screening protocol in healthy young adults without history of syncope. Following brachial arterial catheter insertion, 120 subjects (age 18-40, 72 females, Caucasian) underwent 5min 60° HUT. Polymorphisms tested were: Ser49/Gly and Arg389/Gly in ADRB1; and Arg16/Gly, Gln27/Glu, and Thr164/Ile in ADRB2. Three statistical models (recessive, dominant, additive) were evaluated using general linear models with analysis for each physiologic variable. A recessive model demonstrated a significant association between Arg16/Gly and: absolute supine and upright HR; HUT-induced change in cardiac index (CI), stroke index (SI) and systemic vascular resistance (SVR); and supine and upright norepinephrine values. Blood pressure was not influenced by genotype. Fewer associations were present for other polymorphisms: Ser49/Gly and the change in SI (dominant model), and Arg389/Gly and supine and HUT norepinephrine (additive model). We conclude that in this population, there is a robust association between Arg16/Gly and HUT responses, such that 2 copies of Arg16 increase supine and upright HR, and greater HUT-induced decreases in CI and SI, with greater increases in SVR and norepinephrine. ADRB1 gene variation appears to impact SI and plasma NE levels but not HR. Whether ADRB2 gene variation is ultimately disease-causing or disease-modifying, this study suggests an association between Arg16/Gly and postural hemodynamics, with sympathetic noradrenergic activity affected in a similar direction. This may have implications in the development of orthostatic disorders.
Authors:
E D Wittwer; Z Liu; N D Warner; D R Schroeder; A M Nadeau; A R Allen; C J Murillo; R L Elvebak; B M Aakre; J H Eisenach
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-07-31
Journal Detail:
Title:  Autonomic neuroscience : basic & clinical     Volume:  164     ISSN:  1872-7484     ISO Abbreviation:  Auton Neurosci     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-05     Completed Date:  2012-06-07     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  100909359     Medline TA:  Auton Neurosci     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  89-95     Citation Subset:  IM    
Copyright Information:
Published by Elsevier B.V.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Cardiovascular Diseases / diagnosis*,  genetics*,  metabolism
Female
Genetic Variation
Heart Rate / genetics
Humans
Male
Mass Screening
Norepinephrine / genetics,  metabolism
Polymorphism, Genetic*
Receptors, Adrenergic, beta-1 / genetics*,  physiology
Receptors, Adrenergic, beta-2 / physiology*
Shy-Drager Syndrome / diagnosis*,  genetics*,  metabolism
Stroke / genetics
Young Adult
Grant Support
ID/Acronym/Agency:
1 K12 RR02415-01/RR/NCRR NIH HHS; HL-083947/HL/NHLBI NIH HHS; HL-089331/HL/NHLBI NIH HHS; KL2 RR024151/RR/NCRR NIH HHS; KL2 RR024151-07/RR/NCRR NIH HHS; NS-32352/NS/NINDS NIH HHS; P50 NS032352/NS/NINDS NIH HHS; P50 NS032352-15/NS/NINDS NIH HHS; R01 HL083947/HL/NHLBI NIH HHS; R01 HL083947-05/HL/NHLBI NIH HHS; R01 HL089331/HL/NHLBI NIH HHS; R01 HL089331-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; X4W3ENH1CV/Norepinephrine
Comments/Corrections

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