A deletion in the alpha2B-adrenergic receptor gene and autonomic nervous function in central obesity.
OBJECTIVE
We investigated the impact of a three-amino acid deletion (12Glu9) polymorphism in the alpha(2B)-adrenergic receptor gene on autonomic nervous function. The short form (Glu(9)/Glu(9)) of the polymorphism has previously been associated with a reduced basal metabolic rate in obese subjects. Because autonomic nervous function participates in the regulation of energy metabolism, there could be a link between this polymorphism and autonomic nervous function.


METHODS
Data of a 10-year follow-up study with 126 nondiabetic control subjects and 84 type 2 diabetic patients were used to determine the effects of the 12Glu9 polymorphism on autonomic nervous function. A deep breathing test and an orthostatic test were used to investigate parasympathetic and sympathetic autonomic nervous function. In addition, cardiovascular autonomic function was studied using power spectral analysis of heart rate variability.


RESULTS
No significant differences were found in the frequency of the 12Glu9 deletion polymorphism between nondiabetic and diabetic subjects. The nondiabetic men with the Glu(9)/Glu(9) genotype, especially those with abdominal obesity, had significantly lower total and low-frequency power values in the power spectral analysis when compared with other men. Furthermore, in a longitudinal analysis of 10 years, the decrease in parasympathetic function was greater in nondiabetic men with the Glu(9)/Glu(9) genotype than in the men with the Glu(9)/Glu(12) or Glu(12)/Glu(12) genotypes.


CONCLUSIONS
The results of the present study suggest that the 12Glu9 polymorphism of the alpha(2B)-adrenergic receptor gene modulates autonomic nervous function in Finnish nondiabetic men. In the nondiabetic men with the Glu(9)/Glu(9) genotype, the general autonomic tone is depressed, and vagal activity especially becomes impaired with time. Furthermore, this association is accentuated by central obesity.
Sivenius
Katariina
K
Department of Clinical Nutrition, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. ksiveniu@hytti.uku.fi
Niskanen
Leo
L
Laakso
Markku
M
Uusitupa
Matti
M
D001341:Autonomic Nervous System / Q000503:physiopathology*; D016009:Chi-Square Distribution; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004562:Electrocardiography; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*
C547771:ADRA2B protein, human; D018341:Receptors, Adrenergic, alpha-2; D004247:DNA