E.-C. Långberg and M. Seed Ahmed have contributed equally to this work.
Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes
Version of Record online: 11 JUN 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 8, pages 1720–1725, August 2013
How to Cite
Långberg, E.-C., Seed Ahmed, M., Efendic, S., Gu, H. F. and Östenson, C.-G. (2013), Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes. Obesity, 21: 1720–1725. doi: 10.1002/oby.20162
Disclosure: The authors declared no conflicts of interest.
Funding agencies: This research was supported by The Swedish Research Council, The Swedish Diabetes Association, Novo Nordisk Scandinavia, Novo Nordisk Consortium and The Loo and Hans Osterman Foundation.
- Issue online: 22 AUG 2013
- Version of Record online: 11 JUN 2013
- Accepted manuscript online: 19 NOV 2012 10:50AM EST
- Manuscript Accepted: 1 NOV 2012
- Manuscript Revised: 26 OCT 2012
- Manuscript Received: 12 JUL 2011
- The Swedish Research Council
- The Swedish Diabetes Association
- Novo Nordisk Scandinavia
- Novo Nordisk Consortium
- The Loo and Hans Osterman Foundation
The sympathetic nervous system (SNS) is linked to glucose, lipid, and protein metabolism. The α2A-adrenergic receptor (ADRA2A) is involved in the SNS and mediates inhibition of insulin secretion and lipolysis. The association of ADRA2A single-nucleotide polymorphisms (SNPs) with obesity and/or type 2 diabetes (T2D) was investigated.
Design and Methods
Genotyping was performed in a case–control study of 1,177 Swedish individuals, including lean and obese subjects with normal glucose tolerance (NGT) and T2D patients. ADRA2A mRNA expression was measured in pancreatic islets isolated from T2D patients and nondiabetic subjects.
SNP rs553668 was associated with T2D in men (odds ratio [OR] = 1.47; 95% confidence interval [CI] = 1.08–2.01; P = 0.015) but this association was lost after adjusting for age and for body mass index (BMI). Associations were also detected when comparing obese NGT and lean NGT subjects (OR = 1.49; 95% CI = 1.07–2.07; P = 0.017), and in obese (OR = 1.62; 95% CI = 1.06–2.49; P = 0.026), but not in lean T2D. In women, multiple logistic regression regarding SNP rs521674 demonstrated an increased OR of 7.61 (95% CI = 1.70–34.17; P = 0.008) for T2D when including age as a covariant. Correcting for BMI removed the significant association. When age was included in the model, association also found when obese T2D patients were compared with lean NGT subjects (P = 0.041). ADRA2A mRNA expression in human pancreatic islets was detectable, but with no statistically significant difference between the diabetic and the control groups.
ADRA2A genetic polymorphisms are mainly associated with obesity and possibly with T2D in a Swedish population.