RAPID COMMUNICATIONSExpression of the hepatic Niemann–Pick C1 like 1 protein gene is sensitive to rosuvastatin treatment of primary human hepatocytesBrulhart-Meynet, Marie-Claudea; Deakin, Sara P.a c; Sgroi, Antoninob c; Buhler, Leob c; James, Richard Williama cAuthor Information Departments of aInternal Medicine bSurgery, Cantonal Hospital cMedical Faculty, Geneva University, Geneva, Switzerland Correspondence to Richard William James, PhD, Clinical Diabetes Unit, Department of Internal Medicine, University Hospital, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland Tel: +41 22 372 93 04; fax: +41 22 372 93 26; e-mail: [email protected] Received 9 January 2009 Accepted 2 April 2010 Pharmacogenetics and Genomics: July 2010 - Volume 20 - Issue 7 - p 455-458 doi: 10.1097/FPC.0b013e32833a9328 Buy Metrics Abstract Statins act by reducing hepatic cholesterol synthesis, thus stimulating uptake of serum cholesterol. Statin therapy modulates a number of genes involved in hepatic cholesterol homeostasis. These have rarely been analyzed simultaneously in the same experimental setting, with virtually no studies of primary human hepatocytes. This study analyzed the efficacy of rosuvastatin in the coordinated regulation of a number of genes implicated in cholesterol metabolism in primary human hepatocytes. Expression of five cholesterol-related genes were significantly upregulated, notably the Niemann–Pick C1 like 1 protein, for whom functional studies have been essentially limited to the intestine. Two genes were significantly downregulated, including sterol recognition element binding protein-1 gene that is implicated in control of hepatic lipogenesis. The results show the coordinated regulation of several genes implicated in hepatic cholesterol homeostasis and suggest therapeutic targets that could complement that clinical action of statins. © 2010 Lippincott Williams & Wilkins, Inc.