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J Med Genet 2005;42:402-407 doi:10.1136/jmg.2004.026278
  • Original article

Evidence of an association between genetic variation of the coactivator PGC-1β and obesity

  1. G Andersen1,
  2. L Wegner1,
  3. K Yanagisawa1,
  4. C S Rose1,
  5. J Lin2,
  6. C Glümer1,3,
  7. T Drivsholm3,
  8. K Borch-Johnsen1,3,4,
  9. T Jørgensen3,
  10. T Hansen1,
  11. B M Spiegelman2,
  12. O Pedersen1,4
  1. 1Steno Diabetes Center, Gentofte, Denmark
  2. 2Dana-Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, USA
  3. 3Research Centre for Prevention and Health, Copenhagen County, Glostrup University Hospital, Denmark
  4. 4Faculty of Health Science, University of Aarhus, Denmark
  1. Correspondence to:
 Dr G Andersen
 Steno Diabetes Center, Niels Steensens Vej 2, NSH2.16, DK-2820 Gentofte, Copenhagen, Denmark; gttasteno.dk
  • Received 13 August 2004
  • Accepted 21 November 2004
  • Revised 15 November 2004

Abstract

Background: Peroxisome proliferator activated receptor-γ coactivator-1β (PGC-1β) is a recently identified homologue of the tissue specific coactivator PGC-1α, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1α is involved in adipogenesis, mitochondrial biogenesis, fatty acid β oxidation, and hepatic gluconeogenesis.

Methods: We studied variation in the coding region of human PPARGC1B in Danish whites and related these variations to the prevalence of obesity and type 2 diabetes in population based samples.

Results: Twenty nucleotide variants were identified. In a study of 525 glucose tolerant subjects, the Ala203Pro and Val279Ile variants were in almost complete linkage disequilibrium (R2 = 0.958). In a case–control study of obesity involving a total of 7790 subjects, the 203Pro allele was significantly less frequent among obese participants (p = 0.004; minor allele frequencies: normal weight subjects 8.1% (95% confidence interval: 7.5 to 8.8), overweight subjects 7.6% (7.0 to 8.3), obese subjects 6.5% (5.6 to 7.3)). In a case–control study involving 1433 patients with type 2 diabetes and 4935 glucose tolerant control subjects, none of the examined variants were associated with type 2 diabetes.

Conclusions: Variation of PGC-1β may contribute to the pathogenesis of obesity, with a widespread Ala203 allele being a risk factor for the development of this common disorder.

Footnotes

  • Competing interests: none declared

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