Abstract
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 5 min 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.
Keywords
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Article info
Publication history
Published online: August 02, 2011
Accepted:
July 10,
2011
Received in revised form:
June 8,
2011
Received:
December 30,
2010
Footnotes
☆This work was presented at the 21st Intl. Symposium on the Autonomic Nervous System.
Identification
Copyright
Published by Elsevier Inc.
