Expression of the hepatic Niemann-Pick C1 like 1 protein gene is sensitive to rosuvastatin treatment of primary human hepatocytes.

Marie-Claude Brulhart-Meynet, Sara P Deakin, Antonino Sgroi, Leo Buhler, Richard William James

Department of Internal Medicine, Cantonal Hospital, Geneva, Switzerland.

Pharmacogenetics and genomics 2010 Jul

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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.

Citation

Marie-Claude Brulhart-Meynet, Sara P Deakin, Antonino Sgroi, Leo Buhler, Richard William James. Expression of the hepatic Niemann-Pick C1 like 1 protein gene is sensitive to rosuvastatin treatment of primary human hepatocytes. Pharmacogenetics and genomics. 2010 Jul;20(7):455-8