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

Arterioscler Thromb Vasc Biol. 2005 Mar;25(3):604-10. doi: 10.1161/01.ATV.0000153141.42033.22. Epub 2004 Dec 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Carotid Artery Diseases / epidemiology
  • Carotid Artery Diseases / genetics*
  • Carotid Artery Diseases / metabolism
  • Cell Line
  • Cross-Sectional Studies
  • Endothelium, Vascular / cytology
  • Female
  • Genotype
  • Humans
  • Hypertension / epidemiology
  • Hypertension / genetics
  • Hypertension / metabolism
  • Ion Channels
  • Macrophages / cytology
  • Male
  • Membrane Transport Proteins / genetics*
  • Membrane Transport Proteins / metabolism
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Polymorphism, Single Nucleotide*
  • Prevalence
  • Reactive Oxygen Species / metabolism
  • Risk Factors
  • Sex Distribution
  • Uncoupling Protein 2


  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • UCP2 protein, human
  • Uncoupling Protein 2