1. Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays
- Author
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David Back, Marta Boffito, Sophie Collot-Teixeira, Laura Waters, Ferruccio De Lorenzo, Carl Fletcher, Anton Pozniak, Saliha Yilmaz, Brian Gazzard, and John L. McGregor
- Subjects
Adult ,Male ,Candidate gene ,Gene expression microarray ,Adolescent ,Microarray ,Bioinformatics ,NCEH1 ,Acetate-CoA Ligase ,Down-Regulation ,Pharmacology ,Peripheral blood mononuclear cell ,ACSS2 ,Genetics ,medicine ,Humans ,Ritonavir ,biology ,Gene Expression Profiling ,PBMC ,Computational Biology ,Dual Specificity Phosphatase 1 ,Lipid metabolism ,HIV Protease Inhibitors ,Biomarker ,Middle Aged ,Sterol Esterase ,Real-time polymerase chain reaction ,Gene Expression Regulation ,Immunology ,Leukocytes, Mononuclear ,biology.protein ,Female ,Carboxylic Ester Hydrolases ,Biomarkers ,medicine.drug - 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 100mg once daily and 100mg 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.
- Published
- 2010
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