Alpha2A adrenergic receptor genetic variation contributes to hyperglycemia after myocardial infarction

Abstract Background Acute myocardial infarction (AMI) is frequently associated with transient hyperglycemia even in patients without pre-existing diabetes. Acute stress can lead to increased blood glucose through the effect of catecholamines on alpha 2A -adrenergic receptors (α 2A -ARs) present in pancreatic islet β-cells. Variation in the gene ( ADRA2A ) that encodes the α 2A -AR affects insulin release and glucose control and may play a particularly important role during times of stress. Methods We performed a retrospective cohort study using de-identified electronic medical records linked to a DNA repository in 521 Caucasians and 55 African-American non-diabetic patients with AMI. We examined the association between admission blood glucose concentrations and ten selected ADRA2A SNPs in Caucasians. Results Three ADRA2A SNPS were associated with stress-induced hyperglycemia in Caucasians. Individuals homozygous for the rs10885122 variant (n=9) had a 23% lower admission glucose (geometric mean [95% CI], 99 [83–118]mg/dl) compared with non-carriers (121 [118–125] mg/dl; n=401; P=0.001). Admission glucose was 14% higher in rs1800544 variant homozygotes (134 [119–150]mg/dl; n=36) compared to non-carriers (118 [115–121]mg/dl; n=290, P=0.046). Furthermore, homozygotes of the rs553668 variant (n=13) had a 13% higher glucose (133 [110–160]mg/dl) compared to non-carriers (118 [115–122]mg/dl; n=366; P=0.056). Haplotypes including these ADRA2A SNPs were associated with higher admission glucose levels. Conclusions Three ADRA2A genetic variants are associated with blood glucose and stress-induced hyperglycemia after AMI in Caucasians.