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PLoS One. 2019 Dec 17;14(12):e0226573. doi: 10.1371/journal.pone.0226573. eCollection 2019.

Dysregulation of sterol regulatory element-binding protein 2 gene in HIV treatment-experienced individuals.

Author information

1
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
2
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
3
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
4
School of Public Health, Yale University, New Haven, Connecticut, United States of America.

Abstract

Although antiretroviral therapy (ART) has resulted in a marked decrease in AIDS-related morbidity and mortality, the therapeutic benefit is often limited by side effects such as metabolic derangement such as lipodystrophy and hyperlipidemia and cardiovascular diseases. These side effects are pervasive in people living with HIV (PLWH). However, the underlying mechanisms are not completely understood. We investigated the effects of ART on cholesterol biosynthesis genes. This is a retrospective analysis of data and specimens collected during a cross-sectional, case-control study of ART-induced toxicity. Cases were HIV treatment-experienced individuals with HIV viral suppression and no diagnosis of ART-associated toxicity (n = 18), and controls were HIV-uninfected individuals (n = 18). The mRNA expressions of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and ATP binding cassette transporter A1 (ABCA1) were significantly upregulated in cases (HIV+) compared to controls (HIV-), as well as the corresponding protein expression level of HMGCR. We observed dysregulation between sterol regulatory element-binding protein 2 (SREBP-2, sensory control) and HMGCR and low-density lipoprotein receptor (LDLR) pathways. Dysregulation of cholesterol biosynthesis genes may predate clinical manifestation of ART-induced lipid abnormalities.

Conflict of interest statement

The authors have declared that no competing interests exist.

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