Rs553668

In "Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: a meta-analysis." a meta-analysis of publications prior to September 2012 showed no overall association between rs553668 and T2D risk, but did find an association with very high (poor) P-value for Europeans under recessive gene model (GT=AA, OR=1.36, p=0.02, 95% CI: 1.05, 1.76).

In "Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes." rs553668 was found to correlate with obesity in Swedish population, but not significantly for BMI-corrected T2D risk. ADRA2A is involved in sympathetic nervous system's inhibition of insulin secretion and lipolysis, so direct effect on T2D is usually sought, but the Swedish study suggest it could work through body mass. It also mentions that rs553668 has additionally been reported to be associated with risk of obesity in Caucasians and African Americans, hypertension in African Americans , and with endurance in athletes of Caucasian origin as well as platelet aggregation.

"A single nucleotide polymorphism rs553668 in the ADRA2A gene and the status of Polish elite endurance athletes" also corroborates the link to endurance athletic performance. "Exercise-induced muscle vasodilatation and genetic polymorphisms of alpha-adrenergic receptors, endothelial nitric oxide synthase and bradykinin receptor B2 in individuals without overt heart disease" provides some evidence of a link to vascular function in exercise. "ADRA2A is a cystic fibrosis modifier gene" concludes that rs553668 is modifier of Cystic Fibrosis severity. Genetic polymorphism of the alpha 2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans.

A polymorphism in the alpha2a-adrenoceptor gene and endurance athlete status.

Clinical and pharmacological significance of alpha2-adrenoceptor polymorphisms in cardiovascular diseases.

Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic receptor genes and abdominal fat in the Qu&#233;bec Family Study.

Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations.

A C-1291G polymorphism in the alpha2A-adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels.

A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity.

ADRA2A polymorphisms and ADHD in adults: possible mediating effect of personality.

Genetic variations in the alpha(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine.

Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies.

The rs553668 polymorphism of the ADRA2A gene predicts the worsening of fasting glucose values in a cohort of subjects without diabetes. A population-based study.

Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: a meta-analysis.

Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes.