A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans

Nat Genet. 2001 Jun;28(2):178-83. doi: 10.1038/88911.


Obesity is the most common nutritional disorder in Western society. Uncoupling protein-2 (UCP2) is a recently identified member of the mitochondrial transporter superfamily that is expressed in many tissues, including adipose tissue. Like its close relatives UCP1 and UCP3, UCP2 uncouples proton entry in the mitochondrial matrix from ATP synthesis and is therefore a candidate gene for obesity. We show here that a common G/A polymorphism in the UCP2 promoter region is associated with enhanced adipose tissue mRNA expression in vivo and results in increased transcription of a reporter gene in the human adipocyte cell line PAZ-6. In analyzing 340 obese and 256 never-obese middle-aged subjects, we found a modest but significant reduction in obesity prevalence associated with the less-common allele. We confirmed this association in a population-based sample of 791 middle-aged subjects from the same geographic area. Despite its modest effect, but because of its high frequency (approximately 63%), the more-common risk allele conferred a relatively large population-attributable risk accounting for 15% of the obesity in the population studied.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adipose Tissue / cytology
  • Adipose Tissue / physiology
  • Adult
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Binding Sites
  • Case-Control Studies
  • Cell Line
  • Cross-Sectional Studies
  • DNA-Binding Proteins*
  • Female
  • Gene Frequency
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Haplotypes / genetics
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ion Channels
  • Male
  • Membrane Transport Proteins*
  • Middle Aged
  • Mitochondrial Proteins*
  • Obesity / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Proteins / genetics*
  • Receptors, Aryl Hydrocarbon*
  • Regulatory Sequences, Nucleic Acid
  • Transcription Factors / metabolism
  • Uncoupling Protein 2


  • 3' Untranslated Regions
  • ARNT protein, human
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Proteins
  • Receptors, Aryl Hydrocarbon
  • Transcription Factors
  • UCP2 protein, human
  • Uncoupling Protein 2
  • Aryl Hydrocarbon Receptor Nuclear Translocator