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

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

doi:10.1186/s12879-021-05977-0

Suman Mewa Kinoo, Savania Nagiah + Show 2 more

Open Access

https://doi.org/10.1186/s12879-021-05977-0

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Abstract

BackgroundHIV 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.MethodsThis 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.ResultsCirculating 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.ConclusionsCollectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging, and increasing cholesterol efflux.

Highlights

human immune deficiency virus (HIV) endemic populations are displaying higher incidence of metabolic disorders
The present study sought to evaluate the hepatic expression of genes involved in cholesterol homeostasis (LDLR, Adenosine triphosphate binding cassette A1 (ABCA1), HMGCR) in Black South African HIV positive patients presenting with gallstones relative to HIV negative patients with gallstone disease
The results show that the HIV positive group had a lower Body mass index (BMI) with overall higher levels of total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-c) and significantly higher low-density lipoprotein cholesterol (LDL-c)

Summary

Introduction

HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. Gallstones account for more than 95% of biliary tract diseases in developed countries affecting 20% of the population [1]. Metabolic disorders in developing countries are a growing concern, paralleled with an increase in human immune deficiency virus (HIV) and a consequent judicious roll out of anti-retroviral therapy (ART). Whilst a significant amount of work has linked HIV and ART to altered fat and cholesterol metabolism contributing to metabolic syndrome like effects, diabetes mellitus and cardiovascular disease [4,5,6,7], no studies have looked at gallstone disease in this population. Cholesterol homeostasis is maintained by various endogenous responses involving cholesterol synthesis, transport and excretion [11, 12]

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