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Am. J. Respir. Cell Mol. Biol., Volume 20, Number 2, February, 1999 287-291

Z and S Mutations of the alpha 1-Antitrypsin Gene and the Risk of Chronic Obstructive Pulmonary Disease

Andrew J. Sandford, Tracey D. Weir, John J. Spinelli, and Peter D. Paré

The University of British Columbia Pulmonary Research Laboratory and Health Research Centre, St. Paul's Hospital; and Department of Health Care and Epidemiology, University of British Columbia, Vancouver, British Columbia, Canada

Chronic obstructive pulmonary disease (COPD) has been associated with heterozygosity for the Z and S alleles of the alpha 1-antitrypsin gene in some studies, but these observations have not been confirmed by others. Cigarette smoking is the major risk factor for COPD and may have been a confounding factor in many of the previous studies. We investigated whether the Z or S alleles were more prevalent in a group of heavy smokers with COPD than in a group of nonobstructed smokers. Forced expiratory volume in 1 s and forced vital capacity were derived for 266 patients undergoing lobar or lung resection. These lung-function measurements were used to divide the patients into a COPD group and a group of nonobstructed control subjects. The subjects were typed for the Z and S alleles of the alpha 1-antitrypsin gene using a polymerase chain reaction-based technique. In the COPD patients, 12 of 193 (6%) were heterozygous for the Z allele (MZ) compared with 0 of 73 control subjects, which gave a P value of 0.04 after correction for age, gender, and smoking history. There was no association of the S allele with COPD. The results indicate that the Z, but not the S, allele is a risk factor for COPD in the heterozygous state.




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