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The single‐nucleotide polymorphism ( GPX 4c718t) in the glutathione peroxidase 4 gene influences endothelial cell function: I nteraction with selenium and fatty acids
Author(s) -
Crosley Lynne K.,
Bashir Shabina,
Nicol Fergus,
Arthur John R.,
Hesketh John E.,
Sneddon Alan A.
Publication year - 2013
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201300216
Subject(s) - selenoprotein , single nucleotide polymorphism , gpx1 , glutathione peroxidase , microbiology and biotechnology , phospholipid hydroperoxide glutathione peroxidase , arachidonic acid , biology , endothelial dysfunction , endothelial stem cell , genotype , oxidative stress , chemistry , biochemistry , gene , endocrinology , superoxide dismutase , enzyme , in vitro
Scope Selenium ( S e) is incorporated into selenoproteins as selenocysteine, which requires structures in the 3′‐untranslated region (3′‐ UTR ) of selenoprotein m RNA s. The functional consequences of a single nucleotide polymorphism ( SNP ) within the 3′‐ UTR of the selenoprotein GPX 4 gene ( GPX 4c718t) was assessed in human umbilical vein endothelial cells ( HUVEC s) and monocytes from human volunteers. Methods and results HUVEC and monocytes homozygous for the T ‐ or C ‐variant of the GPX 4c718t SNP were assessed for monocyte–endothelial cell adhesion, expression of VCAM ‐1 and sensitivity to oxidative challenge. Interaction of the SNP with S e 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 S e 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 S e‐dependant changes in lipid peroxide levels and expression of additional selenoproteins. Conclusion These findings demonstrate functional effects of the GPX 4c718t 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.