Abstract
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 tissue1,2. Like its close relatives UCP1 and UCP3, UCP2 uncouples proton entry in the mitochondrial matrix from ATP synthesis1,3 and is therefore a candidate gene for obesity4,5,6. 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 (∼63%), the more-common risk allele conferred a relatively large population-attributable risk accounting for 15% of the obesity in the population studied.
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Acknowledgements
The advice and assistance of P.-K. Pfeiffer in statistical analyses and the technical assistance of D. Pichler is acknowledged. This study was funded by the Austrian Federal Ministry of Science and Transport (GZ 70.063/1-Pr/4/2000) and by a grant from the Medizinische Forschungsgesellschaft Salzburg and the Stiftung Propter Homines, Vaduz, Liechtenstein.
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Esterbauer, H., Schneitler, C., Oberkofler, H. et al. A common polymorphism in the promoter of UCP2 is associated with decreased risk of obesity in middle-aged humans. Nat Genet 28, 178–183 (2001). https://doi.org/10.1038/88911
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DOI: https://doi.org/10.1038/88911
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