| abstract |
The invention provides genes as predictive biomarkers of statin-induced muscle toxicity. Following statin administration, three types of skeletal muscle (soleus, gastrocnemius and extensor digitorum lateralis (EDL)), including fast-twitching and slow-twitching, were profiled and analyzed. Remarkably, for samples exhibiting myopathy, the three muscle types showed highly similar gene expression profiles. Genes involved in oxidation, apoptosis, and ubiquitin-dependent protein catabolism and proteolysis were significantly changed, suggesting extensive protein degradation. In addition, significant induction of genes involved in the regulation of glycolysis and fatty acid oxidation, such as PDK4, 6-phosphofructo-2-kinase, and acetyl-Coenzyme A carboxylase beta, were also observed. PDK4 phosphorylates and inactivates the pyruvate dehydrogenase complex, and is the key inducer of the metabolic switch from glycolysis to fatty acid oxidation. |