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The protease inhibitor PI*S allele and COPD: a meta-analysis

¹ Dept of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark, and ² Channing Laboratory, and ³ Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. ⁴ Authors contributed equally.

CORRESPONDENCE: M. Dahl, Dept of Environmental Health, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115, USA. Fax: 1 6174324710. E-mail: mdahl@hsph.harvard.edu

Keywords: Alpha 1-antitrypsin, chronic obstructive pulmonary disease, emphysema, heterozygote, meta-analysis

Received: November 28, 2004
Accepted March 27, 2005

In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear.

The current authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed.

Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24–8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02–1.38). However, PI MS genotype was not associated with COPD risk after correcting for smoking. Furthermore, mean forced expiratory volume in one second, a measure of airflow obstruction and a defining feature of COPD, did not differ between PI MS and PI MM individuals. There were not enough cases to summarise the risk of COPD in PI SS homozygotes.

In conclusion, the results show that the PI SZ genotype is a significant risk factor for chronic obstructive pulmonary disease. The risk of chronic obstructive pulmonary disease due to the PI MS genotype is not substantially elevated.

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