Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) 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-1 alpha gene lead to a functional consequence in cofactor activity using peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma 2) as interacting transcription factor. Reporter gene assays in HepG2 cells with wildtype and mutant proteins of both PGC1 alpha and PPAR-gamma 2 (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-2 alpha and Pro12Ala polymorphism in PPAR gamma 2 do not affect the functional integrity of these proteins. (c) 2006 Elsevier Inc. All rights reserved.