Activation Of Transposable Elements Upon Statin Treatment
Franco Valdebenito-MaturanaiD, Braulio Valdebenito‐MaturanaiD
Abstract
High cholesterol levels have been associated with cardiovascular diseases, and lowering them has been a key focus in the treatment of such diseases. Statins are drugs used with that aim, and can be divided in the lipophilic Simvastatin and the hydrophilic Rosuvastatin. Regardless of the statin type, a high proportion ([~]70%) of patients stop using statins due to suffering from side effects on skeletal muscle, such as myalgia, and muscle cramps. Thus, there has been a considerable effort in understanding how statins contribute to these side effects. A catalogue of genes and molecular pathways that change upon statin treatment has been recently published, allowing further understanding how the side effects occur. However, Transposable Elements (TEs) were not studied. TEs can move within a genome, and they are highly repetitive, representing about half of the human genome. Currently, most TEs in the human genome are inactive, but it has been shown that TEs can still transcribe, and that either via their transposition or their transcriptional activity, can influence gene expression. Here, using novel computational tools to accurately estimate TE expression, we studied their activity and predicted their potential impact on gene expression. We developed a catalogue of TEs expressed upon statin treatment, and the putative genes whose expression might be influenced by TEs. Overall, we speculate that based on our findings, TEs might be a key target in order to understand statin-mediated side effects.
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