A Deletion in the α_2B‐Adrenergic Receptor Gene and Autonomic Nervous Function in Central Obesity

Abstract

SIVENIUS, KATARIINA, LEO NISKANEN, MARKKU LAAKSO, AND MATTI UUSITUPA. A deletion in the ␣ 2B -adrenergic receptor gene and autonomic nervous function in central obesity. Obes Res. 2003;11:962-970. Objective: We investigated the impact of a three-amino acid deletion (12Glu9) polymorphism in the ␣ 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. Research Methods and Procedures: 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. Discussion: The results of the present study suggest that the 12Glu9 polymorphism of the ␣ 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.

Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene

“…The presence of the del 301-303 allele leads to a small decrease in coupling efficiency resulting in reduced inhibition of adenylyl cyclase (Makaritsis et al 1999). It has been associated with a reduced basal metabolic rate in obese subjects, with an increase in body weight among nondiabetic subjects, and modulation of autonomic nervous function in nondiabetic men (Sivenius et al 2001(Sivenius et al , 2003. However, there is no evidence on the role of this ADRA2B variant in genetic susceptibility to essential hypertension mediated by ADRA2B.…”

α2B-Adrenergic receptor deletion polymorphism and cardiac autonomic nervous system responses to exercise in obese women

“…1 And, a 10-year follow-up study showed that the decrease in parasympathetic function in nondiabetic men with abdominal obesity and impaired cardiac autonomic nervous system (ANS) modulation who were homozygous for Glu 9 /Glu 9 a 2B -AR was greater than the other genotypes. 6 However, these studies provided no information with regard to cardiac autonomic control during physiological maneuvers in obese individuals with 12Glu9 deletion polymorphism of the a 2B -AR gene. It is possible that sympathetic activation may reveal cardiac autonomic alterations that are not apparent at rest.…”

Lack of association between ADRA2B -4825 gene insertion/deletion polymorphism and migraine in Chinese Han population

“…We chose this gene on the basis of its biological relevance. Several reports have revealed associations of various cardiovascular and metabolic phenotypes with ADRA2B +901 indel polymorphism [15][16][17][18][19][20] .…”