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

Saliha Yilmaz; Marta Boffito; Sophie Collot-Teixeira; Ferruccio De Lorenzo; Laura Waters; Carl Fletcher; David Back; Anton Pozniak; Brian Gazzard; John Louis McGregor

doi:10.1016/j.ygeno.2010.03.011

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

Saliha Yilmaz
, Marta Boffito
, Sophie Collot-Teixeira
, Ferruccio De Lorenzo
, Laura Waters
, Carl Fletcher
, David Back
, Anton Pozniak
, Brian Gazzard
, John Louis McGregor

Chelsea & Westminster Hospital NHS Foundation Trust
University of Liverpool
King's College London
PARC Hop Europeen George Pompidou Paris, INSERM

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

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. (C) 2010 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	57 - 65
Number of pages	9
Journal	Genomics
Volume	96
Issue number	1
DOIs	https://doi.org/10.1016/j.ygeno.2010.03.011
Publication status	Published - Jul 2010

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SDG 3 Good Health and Well-being

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10.1016/j.ygeno.2010.03.011

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

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. (C) 2010 Elsevier Inc. All rights reserved.",

author = "Saliha Yilmaz and Marta Boffito and Sophie Collot-Teixeira and \{De Lorenzo\}, Ferruccio and Laura Waters and Carl Fletcher and David Back and Anton Pozniak and Brian Gazzard and McGregor, \{John Louis\}",

year = "2010",

month = jul,

doi = "10.1016/j.ygeno.2010.03.011",

language = "English",

volume = "96",

pages = "57 -- 65",

journal = "Genomics",

publisher = "ACADEMIC PRESS INC",

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T1 - Investigation of low-dose ritonavir on human peripheral blood mononuclear cells using gene expression whole genome microarrays

AU - Yilmaz, Saliha

AU - Boffito, Marta

AU - Collot-Teixeira, Sophie

AU - De Lorenzo, Ferruccio

AU - Waters, Laura

AU - Fletcher, Carl

AU - Back, David

AU - Pozniak, Anton

AU - Gazzard, Brian

AU - McGregor, John Louis

PY - 2010/7

Y1 - 2010/7

N2 - 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. (C) 2010 Elsevier Inc. All rights reserved.

AB - 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. (C) 2010 Elsevier Inc. All rights reserved.

U2 - 10.1016/j.ygeno.2010.03.011

DO - 10.1016/j.ygeno.2010.03.011

M3 - Article

VL - 96

SP - 57

EP - 65

JO - Genomics

JF - Genomics

IS - 1

ER -

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

Abstract

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