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

详细信息    查看全文

• 作者：Saliha Yilmaz ; Marta Boffito ; Sophie Collot-Teixeira ; Ferruccio De Lorenzo ; Laura Waters ; Carl Fletcher ; David Back ; Anton Pozniak ; Brian Gazzard ; John Louis McGregor
• 关键词：PBMC ; Ritonavir ; Gene expression microarray ; Bioinformatics ; Biomarker
• 刊名：Genomics
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：96
• 期：1
• 页码：57-65
• 全文大小：423 K

文摘

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.