title: Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus: associations with obesity indices in middle-aged women.
abstract: Peroxisome proliferator-activated receptor-gamma coactivator-1 (PPARGC1) is a transcriptional coactivator that has been implicated in the regulation of genes involved in energy metabolism. We studied associations of two polymorphisms identified in PPARGC1 transcripts with obesity indices in 591 middle-aged men and 467 middle-aged women of a cross-sectional Austrian population. Because neither polymorphic site was likely to be a functional site, we analyzed sex-specific associations of two loci haplotype combinations with obesity indices. Significant associations with BMI (P = 0.006), waist (P = 0.01) and hip circumference (P = 0.03), and total body fat (P = 0.005) and borderline significant associations with abdominal visceral and subcutaneous fat were observed in women but not men. In women, plasma triglycerides, HDL cholesterol, and glucose significantly differed by haplotype combinations, but these associations were not maintained after statistical consideration of BMI. The haplotype combination of the double-variant allele with the double-wild-type allele was associated with the lowest obesity indices, whereas homozygosity for the double-variant allele was not discriminatory among haplotype combinations. These studies suggest functional differences of PPARGC1 haplotypes in human energy metabolism and support a role of PPARGC1 in obesity.
authors.affiliation: Department of Laboratory Medicine, Landeskliniken Salzburg, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.forename: Hannes
authors.initials: H
authors.lastname: Oberkofler
authors.forename: Veronika
authors.initials: V
authors.lastname: Linnemayr
authors.forename: Bernhard
authors.initials: B
authors.lastname: Iglseder
authors.forename: Margot
authors.initials: M
authors.lastname: Hedegger
authors.forename: Peter
authors.initials: P
authors.lastname: Wolfsgruber
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.forename: Gerd
authors.initials: G
authors.lastname: Fastner
authors.forename: Franz
authors.initials: F
authors.lastname: Krempler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
mesh_terms: D000368:Aged; D002874:Chromosome Mapping; D004734:Energy Metabolism; D005260:Female; D014644:Genetic Variation; D006239:Haplotypes; D006360:Heat-Shock Proteins / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D006360:Heat-Shock Proteins; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1