title: Associations of the UCP2 gene locus with asymptomatic carotid atherosclerosis in middle-aged women.
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.
  
  
  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.
authors.affiliation: Paracelsus Private Medical University and Salzburger Landeskliniken, Salzburg, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Oberkofler
authors.forename: B
authors.initials: B
authors.lastname: Iglseder
authors.forename: K
authors.initials: K
authors.lastname: Klein
authors.forename: J
authors.initials: J
authors.lastname: Unger
authors.forename: M
authors.initials: M
authors.lastname: Haltmayer
authors.forename: F
authors.initials: F
authors.lastname: Krempler
authors.forename: B
authors.initials: B
authors.lastname: Paulweber
authors.forename: W
authors.initials: W
authors.lastname: Patsch
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D002340:Carotid Artery Diseases / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels; D008264:Macrophages / Q000166:cytology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D017678:Sex Distribution; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2