[Development of chronic obstructive pulmonary disease correlates with mini- and microsatellite locus instability].
Allele distribution at a highly polymorphic minisatellite adjacent to the c-Hras1 gene as well as deletions of microsatellite markers, D3S966, D3S1298, D9S171, and a microsatellite within p53 gene, were examined in bronchial epithelium specimens obtained from 53 chronic obstructive pulmonary disease (COPD) patients and healthy donors. A higher frequency of rare Hras1 minisatellite alleles in COPD patients than in the individuals without pulmonary pathology (6.6% versus 2.2%; P < 0.05) was shown. This difference was most pronounced in the group of ten COPD patients with idiopathic pulmonary fibrosis. Three of these patients had rare Hras1 minisatellite allele (P < 0.02 in comparison with healthy controls). Alterations in at least one of the microsatellite markers (deletions or microsatellite instability) were detected in bronchial epithelium samples obtained from: 4 of 10 COPD patients with pneumofibrosis (40%); 15 of 43 COPD patients (34.9%) without pneumofibrosis; and 8 of 20 tobacco smokers (40%) without pulmonary pathology. These defects were not observed in the analogous samples obtained from healthy nonsmoking individuals. No statistically significant differences were revealed between COPD patients and healthy smokers upon comparison of both the total number of molecular defects and the number of defects in the individual chromosomal loci. The total number of molecular defects revealed in bronchial epithelium samples from the individuals of two groups examined correlated with the intensity of exposure to tobacco smoke carcinogens (r = 0.28; P < 0.05). These findings suggest that rare alleles at the Hras1 locus may be associated with hereditary predisposition to COPD and the development of pneumofibrosis, while mutations in microsatellite markers result from exposure to tobacco smoke carcinogens and are not associated with the appearance of these pathologies.
Chizhikov
V V
VV
Research Institute of Carcinogenesis, Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia.
Chikina
S Iu
SIu
Tatosian
A G
AG
Chuchalin
A G
AG
Zborovskaia
I B
IB
D000328:Adult; D000368:Aged; D004276:DNA, Satellite; D016158:Genes, p53; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D018598:Minisatellite Repeats; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000235:genetics; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
D004276:DNA, Satellite