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PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes.

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Author

  • VK Mootha
  • Cecilia Lindgren
  • Karl-Fredrik Eriksson
  • A Subramanian
  • S Sihag
  • J Lehar
  • P Puigserver
  • Emma A Nilsson
  • Martin Ridderstråle
  • Esa Laurila
  • N Houstis
  • MJ Daly
  • N Patterson
  • JP Mesirov
  • TR Golub
  • P Tamayo
  • B Spiegelman
  • ES Lander
  • JN Hirschhorn
  • D Altshuler
  • Leif Groop
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Summary, in English

DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments.

Publishing year

2003

Language

English

Pages

267-273

Publication/Series

Nature Genetics

Volume

34

Issue

3

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes
  • Clinical Medicine
  • Nutrition and Dietetics
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Vascular Diseases - Clinical Research
  • Translational Muscle Research
  • Diabetes - Clinical Obesity

ISBN/ISSN/Other

  • ISSN: 1546-1718