Evidence of an association between genetic variation of the coactivator PGC-1beta and obesity.
BACKGROUND
Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) is a recently identified homologue of the tissue specific coactivator PGC-1alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1alpha is involved in adipogenesis, mitochondrial biogenesis, fatty acid beta 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-1beta may contribute to the pathogenesis of obesity, with a widespread Ala203 allele being a risk factor for the development of this common disorder.
Andersen
G
G
Steno Diabetes Center, Niels Steensens Vej 2, NSH2.16, DK-2820 Gentofte, Copenhagen, Denmark. gtta@steno.dk
Wegner
L
L
Yanagisawa
K
K
Rose
C S
CS
Lin
J
J
Glümer
C
C
Drivsholm
T
T
Borch-Johnsen
K
K
Jørgensen
T
T
Hansen
T
T
Spiegelman
B M
BM
Pedersen
O
O
D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003718:Denmark / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005787:Gene Frequency; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D016601:RNA-Binding Proteins
D002352:Carrier Proteins; C455622:PPARGC1B protein, human; D016601:RNA-Binding Proteins; D005947:Glucose