Abiodun Adefurin1, Leon Darghosian1, Chimalum Okafor1, Vivian Kawai1, Chun Li2, Anushi Shah3, Wei-Qi Wei3, Daniel Kurnik4, C Michael Stein1. 1. Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA. 2. Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, United States. 3. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN, USA. 4. Departments of Medicine and Pharmacology, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA; Clinical Pharmacology Unit, Rambam Medical Center, Haifa, Israel; Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. Electronic address: daniel.kurnik@vanderbilt.edu.
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 alpha2A-adrenergic receptors (α2A-ARs) present in pancreatic islet β-cells. Variation in the gene (ADRA2A) that encodes the α2A-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.
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 alpha2A-adrenergic receptors (α2A-ARs) present in pancreatic islet β-cells. Variation in the gene (ADRA2A) that encodes the α2A-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-diabeticpatients 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.
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