Family study of alpha 1-antitrypsin deficiency: effects of cigarette smoking, measured genotype, and their interaction on pulmonary function and biochemical traits

Genet Epidemiol. 1992;9(5):317-31. doi: 10.1002/gepi.1370090504.


To gain insight into the variable expression of lung disease in alpha 1-antitrypsin (alpha 1AT) deficiency, five quantitative variables including forced expiratory volume at 1 sec (FEV1), forced expiratory flow rate between 25 and 75% of forced vital capacity (FEF25-75), total serum alpha 1AT, oxidized serum alpha 1AT, and total serum immunoglobulin E (IgE) were measured in alpha 1AT deficient individuals and their families. The effect of a known, measured genotype (the Pi type) was estimated for each quantitative trait; the influence of mode of case ascertainment on the measured genotype effect was also assessed. These analyses showed that total alpha 1AT levels are strongly influenced by Pi type; IgE levels are unaffected by Pi type; and FEV1, FEF25-75, and oxidized alpha 1AT are moderately influenced by Pi type. The effect of genotype-by-environment interaction between Pi type and pack-years of cigarette smoking on the five quantitative phenotypes was studied using an analysis of covariance. Significant Pi x pack-years interaction was evident for FEV1, but this effect is confounded in this data set with the Pi x age interaction. Probands who were ascertained because they had chronic obstructive pulmonary disease (COPD) do not demonstrate the significant Pi x pack-years interaction effect of the Pi x pack-years subjects ascertained for other reasons demonstrate. The effect of the Pi x pack-years interaction on FEV1 was no longer significant on a transformed scale, (FEVf12,) thus providing an additive scale for future data analysis. The increased sensitivity of Pi MZ individuals in our sample to cigarette smoking reduced the Pi x packs-years interaction effect on FEF25-75 to borderline significance. This investigation has provided an opportunity to incorporate both measured genotype and genotype-by-environment interaction analyses into the study of the variable expression of lung disease in Pi Z individuals.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Family
  • Female
  • Fluorescent Antibody Technique
  • Genotype
  • Humans
  • Immunoglobulin E / blood
  • Lung Diseases, Obstructive / enzymology
  • Lung Diseases, Obstructive / genetics
  • Male
  • Phenotype
  • Pulmonary Emphysema / enzymology
  • Pulmonary Emphysema / genetics
  • Respiratory Mechanics*
  • Risk Factors
  • Smoking*
  • Surveys and Questionnaires
  • alpha 1-Antitrypsin / genetics*
  • alpha 1-Antitrypsin / metabolism
  • alpha 1-Antitrypsin Deficiency*


  • alpha 1-Antitrypsin
  • Immunoglobulin E