See the published version of this preprint at BMC Infectious Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
Research Article
Savania Nagiah
University of KwaZulu-Natal
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated.
Methods: This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n=5) and HIV negative patients (controls: n=5) were analysed for miR-148a and mRNA expression using quantitative PCR.
Results: Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16±0.64mmol/L) relative to uninfected controls (2.10±0.74mmol/L; p=0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux.
Conclusions: Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging and increasing cholesterol efflux.
Keywords
Gall stone, Cholelithiasis, HIV, cholesterol, LDLr, ABCA1, miR-148a
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Infectious Diseases.
Version 1
Posted 04 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 27 Jan, 2021
Reviews received
Received 25 Jan, 2021
Reviews received
Received 01 Jan, 2021
Reviewers agreed
On 18 Dec, 2020
Reviewers agreed
On 16 Dec, 2020
Reviewers invited
Invitations sent on 02 Dec, 2020
Editor assigned
On 02 Dec, 2020
Editor invited
On 02 Dec, 2020
Submission checks complete
On 02 Dec, 2020
First submitted
On 19 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
Learn more about our company.
A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Infectious Diseases.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research Article
Savania Nagiah
University of KwaZulu-Natal
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Infectious Diseases.
Version 1
Posted 04 Dec, 2020
No community comments so far
Editorial decision: Major revision
On 27 Jan, 2021
Reviews received
Received 25 Jan, 2021
Reviews received
Received 01 Jan, 2021
Reviewers agreed
On 18 Dec, 2020
Reviewers agreed
On 16 Dec, 2020
Reviewers invited
Invitations sent on 02 Dec, 2020
Editor assigned
On 02 Dec, 2020
Editor invited
On 02 Dec, 2020
Submission checks complete
On 02 Dec, 2020
First submitted
On 19 Nov, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Infectious Diseases.
Background: HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated.
Methods: This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n=5) and HIV negative patients (controls: n=5) were analysed for miR-148a and mRNA expression using quantitative PCR.
Results: Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16±0.64mmol/L) relative to uninfected controls (2.10±0.74mmol/L; p=0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux.
Conclusions: Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging and increasing cholesterol efflux.
Figure 1
Figure 1
Figure 2
Figure 2
Figure 3
Figure 3
Loading...