Z and S mutations of the alpha(1)-antitrypsin gene and the risk of chronicobstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) has been associated with heter ozygosity for the Z and S alleles of the alpha(1)-antitrypsin gene in some studies, but these observations have not been confirmed by others. Cigarett e 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 force d vital capacity were derived for 266 patients undergoing lobar or lung res ection. These lung-function measurements were used to divide the patients i nto a COPD group and a group of nonobstructed control subjects, The subject s 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 1 93 (6%) were heterozygous for the Z allele (MZ) compared with 0 of 73 contr ol subjects, which gave a P value of 0.04 after correction for age, gender, and smoking history. Then was no association of the S allele with COPD. Th e results indicate that the Z, but not the S, allele is a risk factor for C OPD in the heterozygous state.