Department of Medical Biochemistry, School of Laboratory Medicine and Medical Science, College of Health Science, University of KwaZulu Natal, Durban, Glenwood, 4041, South Africa.
Discipline of General Surgery, School of Clinical Medicine, College of Health Science, University of KwaZulu Natal, Umbilo, Durban, 4001, South Africa.
BMC Infect Dis. 2021 Mar 23;21(1):294. doi: 10.1186/s12879-021-05977-0.
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.
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.
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.
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.
HIV 流行地区的代谢紊乱发生率较高。HIV 和标准治疗均与脂质和胆固醇代谢改变有关，但在撒哈拉以南非洲人群中，很少研究胆石病（一种与胆固醇相关的疾病）。
本研究旨在评估接受抗逆转录病毒治疗的 HIV 阳性患者中存在胆石症时胆固醇代谢的关键基因（LDLr、HMGCR、ABCA1）和这些基因的转录调节剂（miR-148a、SREBP2）在肝脏中的表达。使用定量 PCR 分析 HIV 阳性患者（病例：n=5）和 HIV 阴性患者（对照：n=5）的肝活检组织中的 miR-148a 和 mRNA 表达。
HIV 阳性组的循环总胆固醇升高，LDL-c 水平显著升高（3.16±0.64mmol/L），与未感染对照组（2.10±0.74mmol/L；p=0.04）相比。该组 LDL-c 的清除受体 LDLr 显著降低（0.18 倍），可能导致 LDL-c 水平升高。LDLr 的转录调节因子 SREBP2 在 HIV 阳性患者中也明显降低（0.13 倍）。调节性 microRNA，miR-148a-3p 在 HIV 阳性患者中减少（0.39 倍），同时靶基因 ABCA1 增加（1.5 倍），调节胆固醇流出。
这些结果表明，接受抗逆转录病毒治疗的 HIV 患者显示出胆固醇代谢基因的肝脏调节改变，减少胆固醇清除，增加胆固醇流出。
