Implications of circadian gene expression in kidney, liver and the effects of fasting on pharmacogenomic studies

Abstract

Pharmacogenomics offers the potential to define metabolic pathways and to provide increased knowledge of drug actions. We studied relative levels of gene expression in the rat using a microarray with 8448 rat UniGenes (1928 known genes, 6520 unknown ESTs) in the liver and kidney as a function of time of day and then of feeding regime, which are common variables in preclinical pharmacogenomic studies. We identified 597 genes, including several key metabolic pathways, whose relative expression levels are significantly affected by time of day: expression of some was further modified by feeding state. These would have sparked interest in a pharmacogenomic study. Our study demonstrates that two common variables in pharmacogenomic studies can have dramatic effects on gene expression. This study provides investigators with baseline information for both kidney and liver with respect to 'normal' changes in gene expression influenced by time of day and feeding state. It also identifies 18 new genes that should be investigated for a role in circadian rhythms in peripheral tissues.