Repository logo
 
Publication

Functional characterization of 16 variants found in the LDL receptor gene

2025-08-12Journal article Open access
Simple item page
datacite.subject.fosCiências Médicas
dc.contributor.authorKonečná, Kateřina
dc.contributor.authorPřerovská, Tereza
dc.contributor.authorLoja, Tomáš
dc.contributor.authorFajkusová, Lenka
dc.contributor.authorKoutná, Jana
dc.contributor.authorKramárek, Michal
dc.contributor.authorAlves, Ana Catarina
dc.contributor.authorBourbon, Mafalda
dc.contributor.authorFreiberger, Tomáš
dc.contributor.authorTichý, Lukáš
dc.date.accessioned2025-12-04T14:58:52Z
dc.date.available2025-12-04T14:58:52Z
dc.date.issued2025-08-12
dc.description.abstractFamilial hypercholesterolemia (FH) is a disorder of cholesterol metabolism characterized by elevated LDL-cholesterol levels. The most common cause of FH is pathogenic variants in the LDL receptor (LDLR) gene. To shed light on the functional impact of selected LDLR variants, we functionally characterized 16 LDLR genetic variants alongside 10 control variants. We performed in vitro assays based on transient expression of WT and mutant LDLRs in LDLR-deficient Chinese hamster ovary cells. We used flow cytometry to analyze the relative amount of LDLRs expressed on the cell surface and the relative amount of internalized LDL. In addition, we analyzed the expression and maturation of LDLR protein by Western blotting. Of the 16 studied variants, two variants (p.(Asn272Thr) and p.(Arg574Leu)) did not exhibit a defect in LDLR function, one variant (p.(Ala540Thr)) exhibited a defect in LDL binding and/or internalization despite normal LDLR cell surface expression, and the remaining 13 variants had a detrimental effect on both LDLR cell surface expression and LDL internalization. The information presented in this study contributes to the clinical classification of LDLR variants and a more precise diagnosis of FH patients, highlighting the type of defect each variant produces.eng
dc.description.sponsorshipThe authors thank Prof Monty Krieger for kindly providing the CHO-ldlA7 cell line. They acknowledge the Flow Cytometry Laboratory at CEITEC MU supported by the EATRIS-ERIC-CZ research infrastructure (grant no.: LM2023053 funded by MEYS CR). Supported by the Ministry of Health of the Czech Republic in cooperation with the Czech Health Research Council under project no.: NU20-02-00261. This work was also supported by the project National Institute for Research of Metabolic and Cardio-vascular Diseases (Programme EXCELES, ID Project No.: LX22NPO5104)—funded by the European Union—Next Generation EU. This work also received funding for the conceptual development of a research organization (University Hospital Brno—FNBr, 65269705) by the Ministry of Health of the Czech Republic. The funders had no role in study design, data collection and analysis, decision to publish, or article preparation.
dc.identifier.citationJ Lipid Res. 2025 Sep;66(9):100873. doi: 10.1016/j.jlr.2025.100873. Epub 2025 Aug 12
dc.identifier.doi10.1016/j.jlr.2025.100873
dc.identifier.eissn1539-7262
dc.identifier.issn0022-2275
dc.identifier.pmid40769381
dc.identifier.urihttp://hdl.handle.net/10400.18/10637
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S002222752500135X?via%3Dihub
dc.relation.ispartofseries100873
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectLDL
dc.subjectLDL/Metabolism
dc.subjectDyslipidemias
dc.subjectFamilial Hypercholesterolemia
dc.subjectFlow Cytometry
dc.subjectFunctional Characterization
dc.subjectLipoproteins
dc.subjectLipoproteins/Receptors
dc.subjectDoenças Cardio e Cérebro-vasculares
dc.titleFunctional characterization of 16 variants found in the LDL receptor gene eng
dc.typejournal article
dcterms.referenceshttps://ars.els-cdn.com/content/image/1-s2.0-S002222752500135X-mmc1.docx
dspace.entity.typePublication
oaire.citation.issue9
oaire.citation.titleJournal of Lipid Research
oaire.citation.volume66
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
AnaCatarinaAlves_artigoint_1-s2.0-S002222752500135X-main.pdf
Size:
3.98 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
4.03 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

DPSPDNT - Artigos em revistas internacionais
INSA - Artigos em revistas internacionais