title: Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies.
abstract: OBJECTIVE
  We quantified the effect of ADRA2A (encoding α-2 adrenergic receptor) variants on metabolic traits and type 2 diabetes risk, as reported in four studies.
  
  
  METHODS
  Genotype data for ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 were analysed in >17,000 individuals (1,307 type 2 diabetes cases) with regard to metabolic traits and type 2 diabetes risk. Two studies (n = 9,437), genotyped using the Human Cardiovascular Disease BeadChip, provided 12 additional ADRA2A SNPs.
  
  
  RESULTS
  Rs553668 was associated with per allele effects on fasting glucose (0.03 mmol/l, p = 0.016) and type 2 diabetes risk (OR 1.17, 95% CI 1.04-1.31; p = 0.01). No significant association was observed with rs10885122. Of the 12 SNPs, several showed associations with metabolic traits. Overall, after variable selection, rs553668 was associated with type 2 diabetes risk (OR 1.38, 95% CI 1.09-1.73; p = 0.007). rs553668 (per allele difference 0.036 mmol/l, 95% CI 0.008-0.065) and rs17186196 (per allele difference 0.066 mmol/l, 95% CI 0.017-0.115) were independently associated with fasting glucose, and rs17186196 with fasting insulin and HOMA of insulin resistance (4.3%, 95% CI 0.6-8.1 and 4.9%, 95% CI 1.0-9.0, respectively, per allele). Per-allele effects of rs491589 on systolic and diastolic blood pressure were 1.19 mmHg (95% CI 0.43-1.95) and 0.61 mmHg (95% CI 0.11-1.10), respectively, and those of rs36022820 on BMI 0.58 kg/m(2) (95% CI 0.15-1.02).
  
  
  CONCLUSIONS
  Multiple ADRA2A SNPs are associated with metabolic traits, blood pressure and type 2 diabetes risk. The α-2 adrenergic receptor should be revisited as a therapeutic target for reduction of the adverse consequences of metabolic trait disorders and type 2 diabetes.
authors: Centre for Cardiovascular Genetics, Department of Medicine, University College London, 5 University St, London, WC1E 6JF, UK. p.talmud@ucl.ac.uk
authors: P J
authors: PJ
authors: Talmud
authors: J A
authors: JA
authors: Cooper
authors: T
authors: T
authors: Gaunt
authors: M V
authors: MV
authors: Holmes
authors: S
authors: S
authors: Shah
authors: J
authors: J
authors: Palmen
authors: F
authors: F
authors: Drenos
authors: T
authors: T
authors: Shah
authors: M
authors: M
authors: Kumari
authors: M
authors: M
authors: Kivimaki
authors: J
authors: J
authors: Whittaker
authors: D A
authors: DA
authors: Lawlor
authors: I N
authors: IN
authors: Day
authors: A D
authors: AD
authors: Hingorani
authors: J P
authors: JP
authors: Casas
authors: S E
authors: SE
authors: Humphries
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics*; D005215:Fasting / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D018341:Receptors, Adrenergic, alpha-2