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The Single-Nucleotide Polymorphism (GPX4c718t) in the Glutathione Peroxidase 4 Gene Influences Endothelial Cell Function: Interaction with Selenium and Fatty Acids

Lookup NU author(s): Lynne Crosley, Professor John Hesketh

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Abstract

ScopeSelenium (Se) is incorporated into selenoproteins as selenocysteine, which requires structures in the 3-untranslated region (3-UTR) of selenoprotein mRNAs. The functional consequences of a single nucleotide polymorphism (SNP) within the 3-UTR of the selenoprotein GPX4 gene (GPX4c718t) was assessed in human umbilical vein endothelial cells (HUVECs) and monocytes from human volunteers. Methods and resultsHUVEC and monocytes homozygous for the T- or C-variant of the GPX4c718t SNP were assessed for monocyte-endothelial cell adhesion, expression of VCAM-1 and sensitivity to oxidative challenge. Interaction of the SNP with Se and different PUFA and effects on selenoprotein expression were also investigated. HUVEC and monocytes homozygous for the T-variant showed elevated adhesion levels compared to cells of the C-variant. This effect was modified by Se and PUFA. HUVEC homozygous for the T-variant showed elevated levels of VCAM-1 protein in the presence of arachidonic acid, were more sensitive to oxidative challenge and showed Se-dependant changes in lipid peroxide levels and expression of additional selenoproteins. ConclusionThese findings demonstrate functional effects of the GPX4c718t SNP in endothelial cells and may suggest that individuals with the TT genotype have impaired endothelial function and are at greater risk of vascular disease compared to individuals with the CC genotype.

Publication metadata

Author(s): Crosley LK, Bashir S, Nicol F, Arthur JR, Hesketh JE, Sneddon AA

Publication type: Article

Publication status: Published

Journal: Molecular Nutrition & Food Research

Year: 2013

Volume: 57

Issue: 12

Pages: 2185-2194

Print publication date: 12/08/2013

ISSN (print): 1613-4125

ISSN (electronic): 1613-4133

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1002/mnfr.201300216

DOI: 10.1002/mnfr.201300216

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