Effect of cigarette smoking on pulmonary function in each phenotype M of alpha-1-protease inhibitor.
Human alpha-1-protease inhibitor (alpha-1-Pi) has been known to be a highly polymorphic protein. We hypothesized that antiprotease activity of each phenotype M of alpha 1-protease inhibitor (PiM) might be different among smokers and that a variation of decrease in pulmonary function for a given amount of cigarette smoking might be associated with PiM phenotypes. To test this, we investigated the effect of cigarette smoking on pulmonary function in each PiM phenotype. The serum level of alpha 1-Pi was measured by the turbidimetric immunoassay and the distribution of PiM phenotypes was determined using isoelectric focusing technique in 247 healthy subjects and 20 COPD patients. Serum levels of alpha-1-antitrypsin of healthy and COPD subjects were 205.1 +/- 31.1 and 179.2 +/- 44.4 (+/- SD) mg/dL, respectively (p > 0.01). The frequency of each PiM phenotype in healthy subjects was shown as follows: M1, 0.555; M1M2, 0.328; M2, 0.041; M1M3, 0.057; M2M3, 0.016; M3, 0.004. The difference in the distribution of PiM phenotypes between healthy and COPD subjects was not significant. Single- and multiple-regression analyses showed that the ratio of FEV1 to forced vital capacity (FVC), in which FEV1 is expressed as percentage of FVC, the maximum flow rate at 50% of FVC divided by measured body height (V50/Ht), and the maximum flow rate at 25% of FVC divided by body height (V25/Ht) were closely related to age and that V25/Ht also was related to smoking index. However, PiM phenotype was unrelated to those pulmonary function variables. We conclude that PiM phenotype is not a major determinant of difference in magnitude of pulmonary impairments caused by cigarette smoking in each individual.
Department of Geriatrics, Faculty of Medicine, University of Tokyo, Japan.
T
T
Matsuse
Y
Y
Fukuchi
H
H
Matsui
E
E
Sudo
T
T
Nagase
H
H
Orimo
D000328:Adult; D000483:Alleles; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007525:Isoelectric Focusing; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012123:Pulmonary Ventilation; D015656:Respiratory Mechanics; D012907:Smoking / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D014797:Vital Capacity; D000515:alpha 1-Antitrypsin / Q000032:analysis / Q000235:genetics*
D000515:alpha 1-Antitrypsin