Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.

Autor: Singh H; Department of Molecular Biology, National AIDS Research Institute, Pune 411026, India. Electronic address: hsingh@nariindia.org., Shyamveer; Department of Molecular Biology, National AIDS Research Institute, Pune 411026, India. Electronic address: shyamveerbharati0@gmail.com., Mahajan SD; Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo's Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA. Electronic address: smahajan@buffalo.edu., Aalinkeel R; Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo's Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA. Electronic address: ra5@buffalo.edu., Kaliyappan K; Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo's Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA. Electronic address: kathirav@buffalo.edu., Schwartz SA; Department of Medicine, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo's Clinical Translational Research Center, 875 Ellicott Street, Buffalo, NY 14203, USA. Electronic address: sasimmun@buffalo.edu., Bhattacharya M; Department of Medicine, ART PLUS CENTRE, Government Medical College & Hospital, University Road, Aurangabad 431004, India. Electronic address: meenakshi.medicine@gmail.com., Parvez MK; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Al-Dosari MS; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2024 Mar 15; Vol. 556, pp. 117830. Date of Electronic Publication: 2024 Feb 13.
DOI: 10.1016/j.cca.2024.117830
Abstrakt: Protease inhibitors (PIs) are associated with an incidence of lipodystrophy among people living with HIV(PLHIV). Lipodystrophiesare characterised by the loss of adipose tissue. Evidence suggests that a patient's lipodystrophy phenotype is influenced by genetic mutation, age, gender, and environmental and genetic factors, such as single-nucleotide variants (SNVs). Pathogenic variants are considered to cause a more significant loss of adipose tissue compared to non-pathogenic. Lipid metabolising enzymes and transporter genes have a role in regulating lipoprotein metabolism and have been associated with lipodystrophy in HIV-infected patients (LDHIV). The long-term effect of the lipodystrophy syndrome is related to cardiovascular diseases (CVDs). Hence, we determined the SNVs of lipid metabolising enzymes and transporter genes in a total of 48 patient samples, of which 24 were with and 24 were without HIV-associated lipodystrophy (HIVLD) using next-generation sequencing. A panel of lipid metabolism, transport and elimination genes were sequenced. Three novel heterozygous non-synonymous variants at exon 8 (c.C1400A:p.S467Y, c.G1385A:p.G462E, and c.T1339C:p.S447P) in the ABCB6 gene were identified in patients with lipodystrophy. One homozygous non-synonymous SNV (exon5:c.T358C:p.S120P) in the GRN gene was identified in patients with lipodystrophy. One novelstop-gain SNV (exon5:c.C373T:p.Q125X) was found in the GRN gene among patients without lipodystrophy. Patients without lipodystrophy had one homozygous non-synonymous SNV (exon9:c.G1462T:p.G488C) in the ABCB6 gene. Our findings suggest that novel heterozygous non-synonymous variants in the ABCB6 gene may contribute to defective protein production, potentially intensifying the severity of lipodystrophy. Additionally, identifying a stop-gain SNV in the GRN gene among patients without lipodystrophy implies a potential role in the development of HIVLD.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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