Change in mRNA Expression after Atenolol, a Beta-adrenergic Receptor Antagonist and Association with Pharmacological Response |
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Authors: | Utkarsh Kohli MD Britney L. Grayson BS Thomas M. Aune PhD Laxmi V. Ghimire MD Daniel Kurnik MD C. Michael Stein MD |
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Affiliation: | Department of Medicine, Division of Clinical Pharmacology, and;Rheumatology, Vanderbilt University, Nashville, TN, USA;;Department of Medicine, Division of Clinical Pharmacology, Chaim Sheba Medical Center, Ramat Gan, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel |
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Abstract: | 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. |
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Keywords: | Atenolol mRNA expression Microarray |
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