Project description:<p>Coronary heart disease (CHD) is an important public health problem in developed countries. Statins are effective in the prevention and treatment of CHD; nevertheless, many patients receiving statins still suffer cardiovascular events (CV) such as heart attack. Identifying genetic variants responsible for differential clinical responses to statins will not only allow individual patients at high residual risk to be targeted for additional therapies, but also will define new biologic pathways contributing to statin response, and thus new targets for future therapies. Accordingly, the goal of this study is to identify genetic variants associated with clinical CV in patients receiving statins.</p> <p>Subjects identified for study are of European descent and include 1718 subjects with CV while on statins (cases) and 4172 subjects without CV while on statins (controls). Key research resources utilized in this effort include VanderbiltD's BioVU DNA databank and associated Synthetic Derivative database of clinical information, and software tools developed to identify drugs and clinical events using Electronic Health Record-derived structured and unstructured ("free text") data. Most cases and controls identified include three data types: ICD-9 codes, medication regimens, and medical test results. Genotyping, using IlluminaD's Infinium HumanOmniExpressExome BeadChip (OmniExpressExome), was performed by the RIKEN Integrative Medical Sciences Center (IMS) and supported by the Pharmacogenomics Research Network (PGRN)-RIKEN IMS Global Alliance.</p>
Project description:We developed a phenotypic screening platform that identified statins as enhancers of immune cell-induced cancer cell death. Statins are currently gaining interest as repurposing candidates for use in oncology as increasing evidence supports that statins exert anti-cancer effects. Considering also our findings, the clinical benefits described for cancer patients receiving statins might be due to a combined effect on both cancer- and immune cells. Studying gene expression profiles is a well established approach for investigating a compound's mode of action. We performed transcriptome-wide gene expression profiling on the human colorectal cancer cell line HCT116-GFP and peripheral blood mononuclear cells (PBMCs). Monocultured and co-cultured cells were treated with DMSO vehicle or pitavastatin (1µM or 10µM) for 24 hours before gene expression was analyzed using a Human Clariom S array.
