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    Genomics. 2010 Jul;96(1):57-65. Epub 2010 Mar 28.

    Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays.

    Source

    Cardiovascular Division, King's College London, 150 Stamford Street, London, UK. saliha.yilmaz@kcl.ac.uk

    Abstract

    Ritonavir is a protease inhibitor associated with metabolic abnormalities and cardiovascular disease. We have investigated the effects of low-dose ritonavir treatment on gene expression in peripheral blood mononuclear cells (PBMC) of 10 healthy donors. Results using whole genome Illumina microarrays show that ritonavir modulates a number of genes implicated in lipid metabolism, inflammation and atherosclerosis. These candidate genes are dual specificity phosphatase 1 DUSP1), Kelch domain containing 3 (KLHDC3), neutral cholesterol ester hydrolase 1 (NCEH1) and acyl-CoA synthetase short-chain family member 2 (ACSS2). Validation experiments using quantitative PCR showed that ritonavir (at 100 mg once daily and 100 mg twice daily significantly down-regulated these 4 selected candidate genes in 20 healthy individuals. Lower expression levels of these 4 candidate genes, known to play a critical role in inflammation, lipid metabolism and atherosclerosis, may explain ritonavir adverse effects in patients.

    Copyright (c) 2010 Elsevier Inc. All rights reserved.

    PMID:
    20353815
    [PubMed - indexed for MEDLINE]

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