Z and S mutations of the alpha1-antitrypsin gene and the risk of chronic obstructive pulmonary disease

Am J Respir Cell Mol Biol. 1999 Feb;20(2):287-91. doi: 10.1165/ajrcmb.20.2.3177.


Chronic obstructive pulmonary disease (COPD) has been associated with heterozygosity for the Z and S alleles of the alpha1-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 alpha1-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Base Sequence
  • DNA Primers
  • Female
  • Heterozygote
  • Humans
  • Lung Diseases, Obstructive / genetics*
  • Lung Diseases, Obstructive / physiopathology
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Respiratory Function Tests
  • Risk Factors
  • alpha 1-Antitrypsin / genetics*


  • DNA Primers
  • alpha 1-Antitrypsin