Expression profiling by high throughput sequencing and transcriptome-wide association study study the metabolic mechanism of the formation of atorvastatin lactone and the risk to statin-induced myotoxicity. Homo sapiens

Statin-induced myotoxicity (SIM) is one of the principal reasons for atorvastatin (AT) non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. To date, the genetic mechanism of SIM is far from well-illustrated. Published data in vitro and in vivo indicated that atorvastatin lactone (ATL) is the key metabolite to induce myotoxicity. We therefore hypothesis that genetic variants increasing the formation of ATL can increase the risk to statin-induced myotoxicity. And a transcriptome-wide association study (TWAS) integrating genome wide variants and gene expression data will applied to identify expression quantitative trait loci (eQTL) associated with the formation of ATL and different bioinformatic tools will then be applied to reveal the potential causal impact of eQTLs on the formation of ATL. Overall design: Liver mRNA profiles of 26 non-liver-cancer and 27 liver-cancer patients were generated by deep sequencing, in triplicate, using Illumina HiSeqTM 2000