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Diabetes 51:1281-1286, 2002
© 2002 by the American Diabetes Association, Inc.


Brief Genetics Reports

Peroxisome Proliferator-Activated Receptor-{gamma} Coactivator-1 Gene Locus

Associations With Obesity Indices in Middle-Aged Women

Harald Esterbauer1, Hannes Oberkofler1, Veronika Linnemayr1, Bernhard Iglseder2, Margot Hedegger3, Peter Wolfsgruber4, Bernhard Paulweber3, Gerd Fastner1, Franz Krempler5, and Wolfgang Patsch1

1 Department of Laboratory Medicine, Landeskliniken Salzburg, Austria
2 Department of Neurology, Landeskliniken Salzburg, Austria
3 First Department of Internal Medicine, Landeskliniken Salzburg, Austria
4 Department of Neuroradiology, Landeskliniken Salzburg, Austria
5 Department of Internal Medicine, Krankenhaus Hallein, Austria

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.



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