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. 2005 May;42(5):402–407. doi: 10.1136/jmg.2004.026278

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

G Andersen 1, L Wegner 1, K Yanagisawa 1, C Rose 1, J Lin 1, C Glumer 1, T Drivsholm 1, K Borch-Johnsen 1, T Jorgensen 1, T Hansen 1, B Spiegelman 1, O Pedersen 1
PMCID: PMC1736055  PMID: 15863669

Abstract

Background: Peroxisome proliferator activated receptor-γ coactivator-1ß (PGC-1ß) 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 ß 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-1ß may contribute to the pathogenesis of obesity, with a widespread Ala203 allele being a risk factor for the development of this common disorder.

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Selected References

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