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


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.

  • BMI, body mass index
  • LD, linkage disequilibrium
  • MAF, minor allele frequency
  • MALDI-TOF, matrix assisted laser desorption/ionisation time of flight
  • NGT, normal glucose tolerant
  • OGTT, oral glucose tolerance test
  • OHA, oral hypoglycaemic agent
  • PERC, PGC-1 related estrogen receptor coactivator
  • PGC, peroxisome proliferator activated receptor-γ coactivator
  • PPAR, peroxisome proliferators activated receptor
  • SNP, single nucleotide polymorphism
  • SSCP, single strand conformational polymorphism
  • WAT, white adipose tissue
  • WHO, World Health Organization
  • obesity
  • diabetes
  • PGC-1β
  • mutation

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