NEW YORK (Reuters Health) - A polymorphism in the alpha-2c-adrenoreceptor common among African-Americans is associated with increased sympathetic nervous and adrenomedullary hormonal activities, a research team has found. This increased activity may account for the increased risk of heart failure among African-Americans, and may predispose carriers to mood disorders.
“Alpha-2 adrenoreceptor is the key regulator for norepinephrine release,” lead investigator Dr. Alexander Neumeister told Reuters Health. “When norepinephrine is released it binds to this receptor, and the receptor signals to stop further release of norepinephrine, so basically it is a feedback loop.”
Dr. Neumeister, at Yale University School of Medicine in West Haven, Connecticut, and his associates recruited 29 healthy African-Americans for their study, 11 of whom were homozygous carriers of the polymorphism, alpha-2c-Del322-325. Nine were heterozygous carriers and nine were non-carriers.
The participants were infused with tritium-labeled noradrenaline and adrenaline, and rates of entry of endogenous noradrenaline and adrenaline into the arterial plasma (spillover) were measured in serial blood samples, using tracer dilution techniques.
Homozygous carriage of the polymorphism was associated with increased noradrenaline and adrenaline spillover compared with heterozygous carriers and noncarriers, the researchers report in the March issue of Pharmacogenetics and Genomics.
The investigators also measured catecholamine levels after administration of yohimbine, a medication that stimulates catecholamine release. For up to 60 minutes after its administration, yohimbine treatment was associated with higher noradrenaline spillover and heart rate, and anxiety as assessed by a visual analog scale was significantly higher for 15 minutes, in homozygotes than in the other groups.
The prolonged release of norepinephrine “means that people who have this polymorphic receptor have a lifelong increased exposure to norepinephrine which probably is not very healthy,” Dr. Neumeister said.
The genetic variant is much more prevalent among African-Americans, he noted, and results of the study may explain this group’s higher rates of hypertension and congestive heart failure.
Moreover, a number of mood and anxiety disorders -- such as panic disorder and major depression -- are associated with increased norepinephrine function.
Dr. Neumeister’s group has found that in patients with depression or anxiety disorder “rates of this receptor polymorphism, even among Caucasians, is much higher than in people who do not have mood and anxiety disorders.”
The researcher concluded by pointing out another connection. “We know that depression is associated with a high risk of heart disease. This may be the common mechanism that underlies this increased risk.”
Pharmacogenetics and Genomics 2005;15.
MeSH Headings:Membrane Proteins: Receptors, Adrenergic: Receptors, Adrenergic, alpha: Receptors, Cell Surface: Panic Disorder: Receptors, Neurotransmitter: Receptors, Biogenic Amine: Receptors, CatecholamineCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
