Journal Article

Hepatic expression of cholesterol regulating genes favour increased circulating low-density lipoprotein in HIV infected patients with gallstone disease: a preliminary study

Nagiah, Savania, Chuturgoon, Anil A., Kinoo, Suman Mewa, Singh, Bugwan

2021

Overview

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 ± 0.64 mmol/L) relative to uninfected controls (2.10 ± 0.74 mmol/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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ABCA1 / ABCA1 protein / Adult / Anti-HIV Agents - therapeutic use / Antiretroviral agents / Antiretroviral drugs / Antiretroviral therapy / ATP Binding Cassette Transporter 1 - genetics / ATP Binding Cassette Transporter 1 - metabolism / ATP-binding protein / Calculi / Cholecystectomy / Cholelithiasis / Cholelithiasis - drug therapy / Cholelithiasis - etiology / Cholelithiasis - genetics / Cholelithiasis - metabolism / Cholesterol / Cholesterol - metabolism / Cholesterol, LDL / Complications and side effects / Diabetes / Disease / Efflux / Ethnicity / Family medical history / Female / Gall stone / Gallstones / Gene expression / Gene Expression Regulation / Gene regulation / Genes / Genetic aspects / Health aspects / HIV / HIV infection / HIV Infections - complications / HIV Infections - drug therapy / HIV Infections - genetics / HIV Infections - metabolism / Homeostasis / Human immunodeficiency virus / Humans / Hypertension / Infectious Diseases / Internal Medicine / LDLr / Lipid metabolism / Lipid Metabolism - genetics / Lipids / Lipoproteins / Lipoproteins, LDL - blood / Liver / Liver - metabolism / Low density lipoprotein / Low density lipoprotein receptors / Medical Microbiology / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Metabolic disorders / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / Middle Aged / miRNA / Parasitology / Population studies / Populations / Receptors, LDL - genetics / Receptors, LDL - metabolism / Research Article / Ribonucleic acid / Risk factors / RNA / Scavenging / Sterol Regulatory Element Binding Protein 2 - genetics / Sterol Regulatory Element Binding Protein 2 - metabolism / Transcription / Tropical Medicine