Analysis of PGC-1alpha variants Gly482Ser and Thr612Met concerning their PPARgamma2-coactivation function.
Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) is a cofactor involved in adaptive thermogenesis, fatty acid oxidation, and gluconeogenesis. Dysfunctions of this protein are likely to contribute to the development of obesity and the metabolic syndrome. This is in part but not definitely confirmed by results of population studies. The aim of this study was to investigate if common genetic variants rs8192678 (Gly482Ser) and rs3736265 (Thr612Met) in the PGC-1alpha gene lead to a functional consequence in cofactor activity using peroxisome proliferator-activated receptor-gamma 2 (PPARgamma2) as interacting transcription factor. Reporter gene assays in HepG2 cells with wildtype and mutant proteins of both PGC1alpha and PPARgamma2 (Pro12Ala, rs1801282) using the acyl-CoA-binding protein (ACBP) promoter showed no difference in coactivator activity. This is the first study implicating that the Gly482Ser and Thr612Met polymorphisms in PGC-1alpha and Pro12Ala polymorphism in PPARgamma2 do not affect the functional integrity of these proteins.
Nitz
Inke
I
Molecular Nutrition, Christian-Albrechts-University of Kiel, Kiel, Germany. initz@molnut.uni-kiel.de
Ewert
Agnes
A
Klapper
Maja
M
Döring
Frank
F
D002460:Cell Line; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D047495:PPAR gamma / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D013912:Threonine / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D006360:Heat-Shock Proteins; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D013912:Threonine; D005998:Glycine