Effect of the alpha2C-adrenoreceptor deletion322-325 variant on sympathetic activity and cardiovascular measures in healthy subjects.
BACKGROUND
The alpha2C-adrenergic receptor plays an important role in the regulation of the sympathetic nervous system and, therefore, blood pressure and heart rate. A deletion polymorphism in its gene (ADRA2C del322-325), ten times more common in black than white Americans, has been associated with a loss of function in vitro and, under controlled study conditions, raised blood pressure and catecholamine secretion. We therefore examined the hypothesis that the ADRA2C deletion variant would alter sympathetic activity and contribute to ethnic differences in blood pressure.


METHODS
We measured resting plasma norepinephrine and epinephrine concentrations, blood pressure and heart rate in 224 healthy subjects (127 whites), and determined their ADRA2C del322-325 genotype. Additionally, we analyzed heart rate variability (HRV) in a subgroup of 50 black subjects.


RESULTS
Systolic (SBP) and diastolic blood pressure (DBP) were higher in blacks than whites [difference (95% confidence interval), 4.4 (1.5-7.4) mmHg, P = 0.003; and 2.7 (0.7-4.6) mmHg, P = 0.01, respectively]. Norepinephrine concentrations did not differ among subjects with 0, 1 and 2 copies of the deletion variant [median (interquartile range), 185.0 (147.5-269.8), 200.0 (154.9-257.0) and 173.8 (158.5-235.8) pg/ml, respectively; P = 0.54]. Similarly, none of the HRV parameters differed among the genotype groups. In multiple linear regression analyses adjusting for multiple covariates, the deletion genotype was not associated with SBP or DBP. In contrast, black ethnicity was associated with higher SBP (P = 0.001) and DBP (P = 0.005).


CONCLUSIONS
The ADRA2C deletion polymorphism had no effect on markers of resting sympathetic activity and cardiovascular measures, and did not account for ethnic differences in blood pressure.
Kurnik
Daniel
D
Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA.
Muszkat
Mordechai
M
Friedman
Eitan A
EA
Sofowora
Gbenga G
GG
Diedrich
André
A
Xie
Hong-Guang
HG
Harris
Paul A
PA
Choi
Leena
L
Wood
Alastair J J
AJ
Stein
C Michael
CM
D000328:Adult; D001741:Black or African American / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics; D004837:Epinephrine / Q000097:blood; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D006339:Heart Rate / Q000235:genetics; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010641:Phenotype; D011110:Polymorphism, Genetic; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012016:Reference Values; D012107:Research Design; D012146:Rest; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000502:physiology*; D013714:Tennessee; D044465:White People / Q000235:genetics
D015415:Biomarkers; D018341:Receptors, Adrenergic, alpha-2; D009638:Norepinephrine; D004837:Epinephrine