on December 16, 2004
Published online before print December 16, 2004, doi: 10.1161/01.ATV.0000153141.42033.22
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 19, 2004
Accepted on December 1, 2004
Associations of the UCP2 Gene Locus With Asymptomatic Carotid Atherosclerosis in Middle-Aged Women
H. Oberkofler ;
From the Paracelsus Private Medical University and Salzburger Landeskliniken (H.O., B.I., K.K., J.U., B.P., W.P.), Salzburg; Konventhospital Barmherzige Brueder (M.H.), Linz; and Krankenhaus Hallein (F.K.), Hallein, Austria.
* To whom correspondence should be addressed. E-mail: w.patsch{at}lks.at.
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 
-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 1
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.
Key words: reactive oxygen species • uncoupling protein • single nucleotide polymorphism • gene expression • haplotype
This article has been cited by other articles:
 |
|
 |
|
  D. X. Zhang and D. D. Gutterman Mitochondrial reactive oxygen species-mediated signaling in endothelial cells Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2023 - H2031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Iglseder, H. Oberkofler, T. K. Felder, K. Klein, B. Paulweber, F. Krempler, D. A. Tregouet, and W. Patsch Associations of PPARGC1A Haplotypes With Plaque Score but Not With Intima-Media Thickness of Carotid Arteries in Middle-Aged Subjects Stroke, September 1, 2006; 37(9): 2260 - 2265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Gable, J. W. Stephens, J. A. Cooper, G. J. Miller, and S. E. Humphries Variation in the UCP2-UCP3 Gene Cluster Predicts the Development of Type 2 Diabetes in Healthy Middle-Aged Men. Diabetes, May 1, 2006; 55(5): 1504 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Bai, H. Onuma, X. Bai, A. V. Medvedev, M. Misukonis, J. B. Weinberg, W. Cao, J. Robidoux, L. M. Floering, K. W. Daniel, et al. Persistent Nuclear Factor-{kappa}B Activation in Ucp2-/- Mice Leads to Enhanced Nitric Oxide and Inflammatory Cytokine Production J. Biol. Chem., May 13, 2005; 280(19): 19062 - 19069. [Abstract] [Full Text] [PDF]
|
|