Hepatic Expression of Cholesterol Regulating Genes Favour Increased Circulating Low-Density Lipoprotein in HIV Infected Patients With Gallstone Disease: A Preliminary Study

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.