The single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene influences endothelial cell function: Interaction with selenium and fatty acids
Article first published online: 12 AUG 2013
© 2013 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Molecular Nutrition & Food Research
Volume 57, Issue 12, pages 2185–2194, December 2013
How to Cite
Crosley, L. K., Bashir, S., Nicol, F., Arthur, J. R., Hesketh, J. E. and Sneddon, A. A. (2013), The single-nucleotide polymorphism (GPX4c718t) in the glutathione peroxidase 4 gene influences endothelial cell function: Interaction with selenium and fatty acids. Mol. Nutr. Food Res., 57: 2185–2194. doi: 10.1002/mnfr.201300216
- Issue published online: 4 DEC 2013
- Article first published online: 12 AUG 2013
- Manuscript Accepted: 9 JUN 2013
- Manuscript Revised: 30 MAY 2013
- Manuscript Received: 22 MAR 2013
- Wellcome Trust. Grant Number: 083358/Z/07/Z
- Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS)
- Glutathione peroxidase 4;
- Single nucleotide polymorphism
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.
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.