Mutation in the 3' region of the alpha-1-antitrypsin gene and chronic obstructive pulmonary disease.

A mutation in the 3' flanking region of the alpha-1-antitrypsin gene has been reported to be associated with chronic obstructive pulmonary disease (COPD). We have investigated the prevalence of this mutation in a group of 185 patients with airway obstruction and in 69 non-obstructed controls. The subjects were selected on the basis of their development of lung cancer and therefore had similar exposure to cigarette smoke, the major risk factor for COPD. In the majority of subjects, the level of airway inflammation and loss of elastic recoil was known, and therefore we were able to test whether the mutation was associated with one of these pathological mechanisms. The prevalence of heterozygotes for the mutation was 10% in both the obstructed group and controls. The mutation was not associated with increased airway inflammation or loss of elastic recoil. This result indicates that the 3' mutation is not a significant risk factor for COPD in this population, and suggests heterogeneity in the pathogenesis of the disease.