Genetic Architecture of the APM1 Gene and Its Influence on Adiponectin Plasma Levels and Parameters of the Metabolic Syndrome in 1,727 Healthy Caucasians

  1. Iris M. Heid12,
  2. Stefanie A. Wagner13,
  3. Henning Gohlke1,
  4. Bernhard Iglseder4,
  5. Jakob C. Mueller5,
  6. Paula Cip3,
  7. Günther Ladurner4,
  8. Raphael Reiter3,
  9. Andreas Stadlmayr3,
  10. Vitolds Mackevics3,
  11. Thomas Illig1,
  12. Florian Kronenberg6 and
  13. Bernhard Paulweber3
  1. 1GSF-National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany
  2. 2Department of Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
  3. 3First Department of Internal Medicine, St. Johann Spital, Paracelsus Private Medical University Salzburg, Salzburg, Austria
  4. 4Department of Neurology, Paracelsus Private Medical University Salzburg, Salzburg, Austria
  5. 5Institute for Medical Statistics and Epidemiology & Institute for Psychiatry and Psychotherapy, Clinic “Rechts der Isar,“ Technical University, Munich, Germany
  6. 6Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
  1. Address correspondence and reprint requests to Florian Kronenberg MD, Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria. E-mail: florian.kronenberg{at}i-med.ac.at

Abstract

The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.

Footnotes

  • I.M.H. and S.A.W. have contributed equally to this article.

    Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

    • Accepted October 19, 2005.
    • Received June 9, 2005.
« Previous | Next Article »Table of Contents

This Article

  1. doi: 10.2337/diabetes.55.02.06.db05-0747 Diabetes February 2006 vol. 55 no. 2 375-384
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)
  4. Online-Only Appendix

Current Issue

  1. November 2009, 58 (11)
    Current Issue
  1. Alert me to new issues of Diabetes