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Glucocorticoid receptor gene, low-grade inflammation, and heart failure: the Heart and Soul study

Christian Otte1, Stefan Wüst, Shoujun Zhao

  • 1Department of Psychiatry, University Medical Center, 20246 Hamburg-Eppendorf, Germany. otte@uke.de

The Journal of Clinical Endocrinology and Metabolism
|April 8, 2010
PubMed

Insights

Glucocorticoid receptor (GR) gene haplotype 3 is linked to increased heart failure (HF) risk and systolic dysfunction in coronary heart disease (CHD) patients. Low-grade inflammation partially explains this association.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • A common glucocorticoid receptor (GR) gene haplotype is linked to coronary heart disease (CHD) susceptibility.
  • The association between this GR haplotype and heart failure (HF) remains uninvestigated.

Purpose of the Study:

  • To determine if GR haplotype 3 is associated with HF.
  • To investigate if low-grade inflammation, measured by C-reactive protein, mediates this association.

Main Methods:

  • Prospective cohort study involving 526 white outpatients with stable CHD.
  • Genotyping for common GR gene polymorphisms and haplotype analysis.
  • Assessment of echocardiographic evidence of ventricular dysfunction, self-reported HF, and HF hospitalizations.

Main Results:

  • Participants with two copies of GR haplotype 3 showed increased likelihood of prevalent HF (HR 4.15) and HF hospitalization (HR 3.0) over 6 years.
  • A trend towards increased systolic dysfunction was observed (HR 3.0).
  • Associations were attenuated after adjusting for C-reactive protein levels, indicating partial mediation by inflammation.

Conclusions:

  • GR gene haplotype 3 is associated with prevalent HF, systolic dysfunction, and subsequent HF hospitalizations in CHD patients.
  • Low-grade inflammation partially mediates the link between GR haplotype 3 and HF.
Abstract

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