Referenced in: none

Automatically associated channels: Kir2.3

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

Authors: H Oberkofler, B Iglseder, K Klein, J Unger, M Haltmayer, F Krempler, B Paulweber, W Patsch

Journal, date & volume: Arterioscler. Thromb. Vasc. Biol., 2005 Mar , 25, 604-10

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15604415

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