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Background: A deteriorating effect of severe alpha(1)-antitrypsin deficiency (ZZ genotype) on lung function is well known, whereas the role of intermediate deficiency (MZ genotype) remains uncertain.Objective: To test the hypothesis that MZ intermediate alpha(1)-antitrypsin deficiency affects pulmonary function and disease.Design: Population-based cohort study with 21-year follow-up.Setting: Copenhagen, Denmark.Participants: 9187 adults randomly selected from the Danish general population.Measurements: Plasma alpha(1)-antitrypsin levels, annual decrease in FEV(1), airway obstruction, and hospitalization and mortality from chronic obstructive pulmonary disease (COPD).Results: 451 participants (4.9%) carried the MZ genotype. Plasma alpha(1)-antitrypsin levels were 31% lower in MZ heterozygotes than in persons with the MM genotype (Student t -test, P < 0.001). Annual decrease in FEV(1) was 25 mL in MZ heterozygotes and 21 mL in persons with the MM genotype (t -test, P = 0.048). Airway obstruction was found in 19% of MZ heterozygotes compared with 15% of MM carriers (chi-square test, P = 0.023); in a logistic regression analysis adjusted for age, sex, and tobacco consumption, the corresponding odds ratio was 1.3 (CI, 1.0 to 1.7). The incidence of hospitalization and mortality from COPD was 32 cases per 10 000 person-years in persons with the MZ genotype and 22 cases per 10 000 person-years in those with the MM genotype (log-rank test, P = 0.063). In a Cox regression model adjusted for age, sex, tobacco use, and FEV(1) at study entry, relative risk for COPD outcomes in persons with the MZ genotype versus persons with the MM genotype was 1.5 (CI, 1.0 to 2.3). All these results were independent of the S and E alleles in this gene and were not affected by cystic fibrosis Delta F508 heterozygosity.Conclusions: MZ heterozygotes had a slightly greater rate of decrease in FEV(1) and were modestly over-represented among persons with airway obstruction and COPD. In the population at large, MZ heterozygosity may account for a fraction of COPD cases---on the order of 2%, similar to the percentage of persons with COPD who have the severe but rare ZZ genotype. [ABSTRACT FROM AUTHOR]

Background: Odds ratios for venous thromboembolism (deep venous thrombosis and pulmonary embolism) derived from case-control studies range from 3 to 16 for heterozygotes compared with noncarriers and up to 79 for homozygotes compared with noncarriers., Objective: To estimate risks for venous thromboembolism in the adult Danish population according to factor V Leiden genotype., Design: Cohort study with 23 years of follow-up., Setting: Adult Danish population., Participants: 9253 randomly selected individuals., Measurements: Hospitalization and death from venous thromboembolism, factor V Leiden genotype, and additional thromboembolic risk factors., Results: Adjusted hazard ratios in heterozygotes and homozygotes compared with noncarriers were 2.7 (95% CI, 1.8 to 3.8) and 18 (CI, 4.1 to 41) for venous thromboembolism overall, 2.4 (CI, 1.3 to 3.8) and 22 (CI, 0 to 60) for deep venous thrombosis, and 3.0 (CI, 1.7 to 4.9) and 11 (CI, 0 to 33) for pulmonary embolism. The lowest absolute 10-year risks for venous thromboembolism in factor V Leiden heterozygotes and homozygotes--0.7% (CI, 0.5% to 1.0%) and 3% (CI, 1% to 8%)--were found in nonsmokers younger than 40 years of age with a body mass index below 25 kg/m2; the corresponding highest risks--10% (CI, 7% to 14%) and 51% (CI, 13% to 100%)--were found in smokers older than 60 years of age with a body mass index above 30 kg/m2., Conclusions: Hazard ratios for venous thromboembolism in factor V Leiden heterozygotes and homozygotes compared with noncarriers in the adult Danish population were approximately 3 and 18, respectively. The simultaneous presence of smoking, obesity, and old age resulted in absolute 10-year thromboembolic risks of 10% in heterozygotes and 51% in homozygotes.