The genetic variant that causes this malfunction is nearly 15 times as prevalent in African-Americans as Caucasians and might explain why African-Americans have a higher rate of congestive heart failure, according to the first author, Alexander Neumeister, M.D., associate professor in the Department of Psychiatry at Yale School of Medicine.
In his study of 29 healthy African-Americans, 11 had the genetic variant, nine were carriers of the genetic variant, and nine were not carriers. Those who tested positive for the genetic variant had elevated norepinephrine levels, heart rate and blood pressure, suggesting impaired receptor function. The effects were more pronounced after the subjects were given a medication that blocked the action of the receptor, causing a sustained release of norepinephrine.
"The subjects had a higher blood pressure response and a higher heart rate," Neumeister said. "They were perfectly normal people, but at baseline and when injected with a medication to block the receptor their test results indicated they might be at higher risk for hypertension. They also were more anxious than people without this genetic variant."
The key regulator of norepinephrine function is the alpha-2 receptor. When norepinephrine is released, it binds to this receptor, sending out a signal to block the release of norepinephrine.
Co-authors included Dennis Charney of Mount Sinai School of Medicine; Inna Belfer, Marilla Geraci, Courtney Holmes, Omer Bonne, David Luckenbaugh, Husseini Manji, David Goldman, and David Goldstein, National Institutes of Health and National Institute of Mental Health; Yehonatan Sharabi, Chaim Sheba Medical Center, Israel, and Tanya Alim, Howard University College of Medicine. The study was funded by the Intramural Program of the National Institute of Mental Health.
Pharmacogenetics and Genomics 15 (3): 143-149 (March 2005).
Journal
Pharmacogenetics and Genomics