Correlation analysis of gene expression and clinical chemistry to identify biomarkers of skeletal myopathy in mice treated with PPAR agonist GW610742X

• Published in: Biomarkers 2008-01, Vol.13 (4), p.364-376
• Main Authors: Casey, W. M., Brodie, T., Yoon, L., Ni, H., Jordan, H. L., Cariello, N. F.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; biomarker; Biomarkers - blood; correlation; Creatine Kinase - blood; Diseases of striated muscles. Neuromuscular diseases; Female; gene expression; Gene Expression - drug effects; Gene Expression Profiling; glycolysis; Male; Medical sciences; Metallothionein - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle Proteins; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Diseases - blood; Muscular Diseases - genetics; myopathy; Neurology; Nuclear Proteins - genetics; Oligonucleotide Array Sequence Analysis; oxidative stress; Peroxisome Proliferator-Activated Receptors - agonists; Peroxisome Proliferator-Activated Receptors - genetics; PPAR; ras Proteins - genetics; Rats; Rats, Sprague-Dawley; Repressor Proteins - genetics; STAT3 Transcription Factor - genetics; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Thiazoles - pharmacology
• ISSN: 1354-750X; 1366-5804
• DOI: 10.1080/13547500801903545

Abstract Data from individual animals were used to identify genes in mouse skeletal muscle whose expression correlated with a known serum marker of skeletal myopathy, creatine kinase activity (CK), after treatment with a peroxisome proliferator-activated receptors (PPAR) agonist, GW610742X. Six genes had correlation coefficients of ≥0.90: Mt1a (metallothionein 1a), Rrad (Ras-related associated with diabetes), Ankrd1 (ankyrin repeat domain 1), Stat3 (signal transducer and activator of transcription 3), Socs3 (suppressor of cytokine signalling 3) and Mid1ip1 (Mid1 interacting protein 1). The physiological function of these genes provides potentially useful information relating to the mechanism of PPAR-induced skeletal myopathy, with oxidative stress and disruption of glycolysis most closely associated with myopathic damage. Some of the muscle genes most highly correlated with serum CK in mice also appear to be good indicators of PPAR-induced myopathy in rat skeletal muscle, demonstrating the translational potential of this approach. This study clearly shows the utility of using correlation analysis as a simple tool for identifying novel biomarkers and investigating mechanisms of toxicity.