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Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis

C P Hersh1, M Dahl, N P Ly

  • 1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harcard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.

Thorax
|September 30, 2004
PubMed
Abstract

Insights

Individuals with alpha-1-antitrypsin deficiency (PI MZ heterozygotes) may have an increased risk of chronic obstructive pulmonary disease (COPD). Further research is needed to confirm this association, especially considering smoking factors.

Area of Science:

  • Pulmonary Medicine
  • Genetics
  • Epidemiology

Background:

  • Severe alpha-1-antitrypsin deficiency (PI ZZ) is a known genetic risk factor for COPD.
  • The COPD risk associated with alpha-1-antitrypsin deficiency heterozygosity (PI MZ) remains debated.

Purpose of the Study:

  • To investigate the association between alpha-1-antitrypsin deficiency heterozygosity (PI MZ) and the risk of COPD.
  • To evaluate lung function (FEV1) in PI MZ individuals.

Main Methods:

  • Systematic literature search of MEDLINE (1966-2003) for studies on PI MZ and COPD risk or FEV1.
  • Meta-analysis of odds ratios (OR) for COPD in PI MZ versus PI MM (normal genotype).
  • Analysis of FEV1 as a continuous outcome in PI MZ versus PI MM.

Main Results:

  • 16 studies reported a combined OR of 2.31 (95% CI 1.60-3.35) for COPD in PI MZ individuals.
  • OR was higher in case-control (2.97) than cross-sectional studies (1.50) and attenuated when adjusted for smoking (1.61).
  • No significant difference in mean FEV1 was observed between PI MM and PI MZ individuals in seven studies.

Conclusions:

  • Case-control studies suggest increased COPD odds in PI MZ individuals, but cross-sectional studies did not confirm this.
  • Study design variability complicates interpretation; results may indicate a small overall risk or a larger risk in a subset.
  • Further research adjusting for smoking and other COPD phenotypes is necessary to definitively determine PI MZ heterozygote risk for COPD.

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