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CHRONIC OBSTRUCTIVE PULMONARY DISEASE |
1-antitrypsin PI MZ heterozygotes: a meta-analysis
1 Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
2 Department of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark
Correspondence to:
Correspondence to:
Dr E K Silverman
Channing Laboratory, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; ed.silverman{at}channing.harvard.edu
Background: Severe 
1-antitrypsin deficiency, usually related to homozygosity for the protease inhibitor (PI) Z allele, is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD). The risk of COPD in PI MZ heterozygous individuals is controversial.
Methods: A search of MEDLINE from January 1966 to May 2003 identified studies that examined the risk of COPD in PI MZ individuals and studies that measured forced expiratory volume in 1 second (FEV1) in heterozygotes.
Results: In 16 studies that reported COPD as a categorical outcome, the combined odds ratio (OR) for PI MZ versus PI MM (normal genotype) was 2.31 (95% CI 1.60 to 3.35). The summary OR was higher in case-control studies (OR 2.97; 95% CI 2.08 to 4.26) than in cross sectional studies (OR 1.50; 95% CI 0.97 to 2.31) and was attenuated in studies that adjusted for cigarette smoking (OR 1.61; 95% CI 0.92 to 2.81). In seven studies that reported FEV1 as a continuous outcome there was no difference in mean FEV1 between PI MM and PI MZ individuals.
Conclusions: Case-control studies showed increased odds of COPD in PI MZ individuals, but this finding was not confirmed in cross sectional studies. Variability in study design and quality limits the interpretation. These results are consistent with a small increase in risk of COPD in all PI MZ individuals or a larger risk in a subset. Future studies that adjust for smoking and include other COPD related phenotypes are required to conclusively determine the risk of COPD in PI MZ heterozygotes.
Keywords: 1-antitrypsin; chronic obstructive pulmonary disease; heterozygote; meta-analysis; genetics
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Thorax 2004 59: 821a.
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