Change in mRNA Expression after Atenolol, a Beta-adrenergic Receptor Antagonist and Association with Pharmacological Response

AIMS: Genetic determinants of variability in response to beta-blockers are poorly characterized. We defined changes in mRNA expression after a beta-blocker to identify novel genes that could affect response and correlated these with inhibition of exercise-induced tachycardia, a measure of beta-blocker sensitivity. METHODS: Nine subjects exercised before and after a single oral dose of 25mg atenolol and mRNA gene expression was measured using an Affymetrix GeneChip Human Gene 1.0 ST Array. The area under the heart rate-exercise intensity curve (AUC) was calculated for each subject; the difference between post- and pre-atenolol AUCs (Delta AUC), a measure of beta-blocker response, was correlated with the fold-change in mRNA expression of the genes that changed more than 1.3-fold. RESULTS: Fifty genes showed more than 1.3-fold increase in expression; 9 of these reached statistical significance (P < 0.05). Thirty-six genes had more than 1.3-fold decrease in expression after atenolol; 6 of these reached statistical significance (P < 0.05). Change in mRNA expression of FGFBP2 and Probeset ID 8118979 was significantly correlated with atenolol response (P = 0.03 and 0.02, respectively). CONCLUSION: The expression of several genes not previously identified as part of the adrenergic signaling pathway changed in response to a single oral dose of atenolol. Variation in these genes could contribute to unexplained differences in response to beta-blockers.