Article Text

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

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.

  • 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

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.