Molecular diagnosis of intermediate and severe alpha(1)-antitrypsin deficiency: MZ individuals with chronic obstructive pulmonary disease may have lower lung function than MM individuals

Background: We tested whether intermediate (MZ, SZ) and severe (ZZ) alpha ( 1)-antitrypsin deficiency affects lung function in the population at large. Methods: We performed spirometry [forced expiratory volume in 1 s (FEV1) an d forced vital capacity (FVC)] and genotyping of 9187 individuals from the adult general population df Copenhagen, Denmark. Results: As expected, the frequencies of individuals with MM, MSI SS, MZ, S Z, and ZZ genotypes were 0.891, 0.054, 0.001, 0.052, 0.001, and 0.001, resp ectively Genotype interacted with clinically established chronic obstructiv e pulmonary disease (COPD) on the percentage of the predicted FEV1 (P = 0.0 04): the percentage of the predicted FEV, was reduced in MZ compared with M M individuals among those with clinically established COPD, but not among t hose without COPD. Furthermore, SZ compound heterozygotes had lower FEV1/FV C ratios than MM individuals (P < 0.05), and ZZ homozygotes had lower perce ntages of the predicted FEV, and FEV1/FVC ratios than MM, MS, SS, and MZ in dividuals (all Ps <0.01). Reduced lung function in SZ and ZZ vs MM individu als could be demonstrated in current and ex-smokers, but not in nonsmokers. Compared with MM individuals in the same groups, FEV, was reduced 655 mt i n MZ individuals with clinically established COPD, 364 mt in SZ current smo kers, and 791 mt in ZZ current smokers. Conclusions: In the population at large, MZ was associated with reduced pul monary function in individuals with clinically established COPD, whereas SZ and ZZ were associated with reduced pulmonary function in smokers. The pre sence of the alpha (1)-antitrypsin MZ genotype may in certain circumstances produce marked aggravation of airway obstruction in individuals prone to d evelop COPD, (C) 2001 American Association for Clinical Chemistry.