Presenting author: Ituro Inoue¹

Email: itinoue@nig.ac.jp

¹National Institute of Genetics, Laboratory of Human Genetics, Japan

The metabolic disruptions resulted from the loss of citrin, including the serious stage citrullinemia type II (CTLN2), have not been fully elucidated. In a comprehensive study of transcriptomes from liver biopsies of CD/CTLN2 patients, we discovered several significant findings. Enrichment analysis of differentially expressed genes provided insights into disrupted lipid metabolism which leads to liver steatosis, enhanced compensatory energy responses, and suppressed signaling pathways in diseased livers. Co-expression analysis revealed gene modules correlated with disease severity, including the increased activity of the ω-oxidation pathway and enhanced immune response. Moreover, analysis of miRNA expression profiles revealed up-regulated miRNAs, such as miR-27a/b and miR-192, which may play a crucial role in modulating lipid metabolism and other metabolic functions. Finally, we explored the connection between CTLN2 with liver cancer using multiple approaches showing an intensified inflammatory response in CD/CTLN2 liver samples, which creates a conducive environment for the development of malignant cells.