Open AccessChange in mRNA Expression after Atenolol, a Beta‐adrenergic Receptor Antagonist and Association with Pharmacological Response
Author(s) -
Kohli Utkarsh,
Grayson Britney L.,
Aune Thomas M.,
Ghimire Laxmi V.,
Kurnik Daniel,
Stein C. Michael
Publication year - 2009
Publication title -
archives of drug information
Language(s) - English
Resource type - Journals
ISSN - 1753-5174
DOI - 10.1111/j.1753-5174.2009.00020.x
Subject(s) - atenolol , gene expression , messenger rna , medicine , endocrinology , adrenergic receptor , gene , receptor , beta (programming language) , antagonist , pharmacology , biology , genetics , blood pressure , computer science , programming language
Aims. Genetic determinants of variability in response to β‐blockers are poorly characterized. We defined changes in mRNA expression after a β‐blocker to identify novel genes that could affect response and correlated these with inhibition of exercise‐induced tachycardia, a measure of β‐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 (Δ AUC), a measure of β‐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 β‐blockers.