title: Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  ADRA2A genetic polymorphisms are mainly associated with obesity and possibly with T2D in a Swedish population.
authors.affiliation: Department of Molecular Medicine and Surgery, Rolf Luft Center for Diabetes Research, Karolinska Institutet, Karolinska University Hospital (Solna), Stockholm, Sweden.
authors.forename: Ewa-Carin
authors.initials: EC
authors.lastname: Långberg
authors.forename: Mohammed
authors.initials: M
authors.lastname: Seed Ahmed
authors.forename: Suad
authors.initials: S
authors.lastname: Efendic
authors.forename: Harvest F
authors.initials: HF
authors.lastname: Gu
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Östenson
mesh_terms: D015992:Body Mass Index; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D013548:Sweden; D044465:White People / Q000235:genetics
chemical_list: C547768:ADRA2A protein, human; D012333:RNA, Messenger; D018341:Receptors, Adrenergic, alpha-2