In "Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: a meta-analysis."[PMID 23462695] 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."[PMID 23526671] 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 [PMID 17512307][PMID 11571596][PMID 11886485], hypertension in African Americans [PMID 15561320], and with platelet aggregation [PMID 8541000].
"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.[PMID 8541000] Genetic polymorphism of the alpha 2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans.
[PMID 11039642] A polymorphism in the alpha2a-adrenoceptor gene and endurance athlete status.
[PMID 15561320] Clinical and pharmacological significance of alpha2-adrenoceptor polymorphisms in cardiovascular diseases.
[PMID 11571596] Interactions among the glucocorticoid receptor, lipoprotein lipase and adrenergic receptor genes and abdominal fat in the Québec Family Study.
[PMID 17512307] Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations.
[PMID 11886485] A C-1291G polymorphism in the alpha2A-adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels.
[PMID 19876010] A preliminary candidate genotype-intermediate phenotype study of satiation and gastric motor function in obesity.
[PMID 20864182] ADRA2A polymorphisms and ADHD in adults: possible mediating effect of personality.
[PMID 21063237] Effect of ADRA2A and BDNF gene-gene interaction on the continuous performance test phenotype
[PMID 21325151] Genetic variations in the alpha(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine.
[PMID 21455730] Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies.
[PMID 22061269] 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.
[PMID 23153004] Evaluation of the Association Between the ADRA2A Genetic Polymorphisms and Type 2 Diabetes in a Chinese Han Population
[PMID 23266789] Adrenergic neurotransmitter system transporter and receptor genes associated with atomoxetine response in attention-deficit hyperactivity disorder children.
[PMID 23462695] Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: a meta-analysis.
[PMID 23466530] SCN1AIVS5-91G>A polymorphism is associated with susceptibility to epilepsy but not with drug responsiveness.
[PMID 23526671] Genetic association of adrenergic receptor alpha 2A with obesity and type 2 diabetes.
|Disease||ALPHA-2A ADRENERGIC RECEPTOR|
|CLNDBN||ALPHA-2A ADRENERGIC RECEPTOR, OVEREXPRESSION or TYPE 2 DIABETES SUSCEPTIBILITY (safer to say the former than the latter)|
|CLNSRC||ClinVar OMIM Allelic Variant|
[PMID 25818344] ADRA2A is involved in neuro-endocrine regulation of bone resorption
[PMID 26410938] [Genetic Association of ADRA2A and ADRB3 Genes with Metabolic Syndrome among the Tatars]
[PMID 26563278] ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer