The single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene influences endothelial cell function: Interaction with selenium and fatty acids

Lynne K Crosley, Shabina Bashir, Fergus Nicol, John R Arthur, John E Hesketh, Alan A Sneddon

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Abstract

Scope
Selenium (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 results
HUVEC 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.

Conclusion
These 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.
Original languageEnglish
Pages (from-to)2185-2194
Number of pages10
JournalMolecular Nutrition & Food Research
Volume57
Issue number12
Early online date12 Aug 2013
DOIs
Publication statusPublished - Dec 2013

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Keywords

  • endothelial
  • glutathione peroxidase 4
  • monocyte
  • selenium
  • single nucleotide polymorphism

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