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Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):604-10. Epub 2004 Dec 16.

Associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women.

Author information

1
Paracelsus Private Medical University and Salzburger Landeskliniken, Salzburg, Austria.

Abstract

OBJECTIVE:

Reactive oxygen species (ROS) contribute to atherogenesis. Uncoupling protein 2 (UCP2) reduces mitochondrial ROS generation and protects against the disease in animal models. A common -866G/A promoter polymorphism that has been associated with obesity and beta-cell function may also affect UCP2 gene expression in cells of the arterial wall.

METHODS AND RESULTS:

Genotype distributions of the -866G/A and of a 45nt-del/ins polymorphism in the 3'-untranslated region of the UCP2 gene were determined in 1334 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR). We observed a modest association of the -866G/A promoter polymorphism and 2-loci haplotypes with asymptomatic carotid atherosclerosis in female study participants. Functional studies revealed increased expression of the -866G wild-type allele in human umbilical vein endothelial cells and differentiated THP-1 cells. Electrophoretic mobility shift assay studies and antibody-interference assays performed with nuclear extracts of various cell lines showed binding of cell-type specific protein complexes to the region encompassing the -866 site and suggested involvement of hypoxia inducible factor 1alpha in the regulation of UCP2 gene expression in endothelial cells and macrophages.

CONCLUSIONS:

Our results suggest a role of UCP2 in atherogenesis as originally proposed from studies in animal and cell culture models.

[Indexed for MEDLINE]

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