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Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages

A M Wood1, C Bassford, D Webster

  • 1School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK. a.m.wood@bham.ac.uk

Thorax
|January 14, 2011
PubMed
Abstract

Insights

Genetic variations in Vitamin D-binding protein (DBP) are linked to chronic obstructive pulmonary disease (COPD). DBP in sputum correlates with macrophage activation, suggesting a role in lung disease pathogenesis.

Area of Science:

  • Pulmonary Medicine
  • Genetics
  • Immunology

Background:

  • Genetic polymorphisms in Vitamin D-binding protein (DBP) have been linked to chronic obstructive pulmonary disease (COPD).
  • DBP plays an indirect role in macrophage activation, suggesting its presence in the airway may contribute to lung disease.
  • This study investigates the hypothesis that DBP in the airway contributes to lung disease through macrophage activation.

Purpose of the Study:

  • To investigate the association between DBP gene polymorphisms and COPD phenotypes.
  • To determine the relationship between DBP levels, vitamin D status, and lung function.
  • To explore the role of DBP in airway inflammation and macrophage activation in COPD patients.

Main Methods:

  • Genotyping of tag single nucleotide polymorphisms (SNPs) in the DBP gene (GC) in 471 subjects with alpha1-antitrypsin deficiency (AATD).
  • Association analysis with COPD phenotypes, including replication in subjects with usual COPD and controls.
  • Measurement of serum vitamin D and DBP, and sputum DBP levels, correlating these with lung function and alveolar macrophage activation.

Main Results:

  • Specific DBP SNPs (rs2070741, rs7041) were associated with airway bacterial colonization and bronchiectasis.
  • The GC2 DBP variant was linked to bronchiectasis in AATD and protected against COPD, a finding replicated in usual COPD patients.
  • Circulating DBP levels inversely correlated with FEV(1), while sputum DBP directly correlated with alveolar macrophage activation.

Conclusions:

  • The genetic association of DBP with COPD may be mediated by its effects on macrophage activation.
  • DBP levels in the airway are related to lung function (FEV(1)) and influence macrophage activation.
  • Vitamin D's effects on lung health may be independent of DBP and more strongly related to innate immunity.

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