pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLCpulmo-3611Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESГетерозиготность по мутации ΔF508 гена муковисцидоза среди больных с хронической обструктивиой патологией органов дыханияThe heterozygosity of the cystic fibrosis gene on ΔF508 mutation in patients with chronic obstructive pulmonary pathologyСамильчукЕ. И.SamilchukE. I.

Москва

ЧучалинА. Г.ChuchalinA. G.

Москва

Институт пульмонологии МЗ РФRussian Federation199430091994034750Copyright © Самильчук Е.И., Чучалин А.Г., 19941994Самильчук Е.И., Чучалин А.Г.Samilchuk E.I., Chuchalin A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/3611

Целью настоящего исследования было изучение частоты встречаемости мутации ΔF508 гена муковисцидоза среди пациентов ХОЗЛ. Обследовано 66 пациентов с ХОЗЛ, 35 пациентов с необструктивными заболеваниями органов дыхания и 35 здоровых добровольцев. Возрастной диапазон составил 17—76 лет.Были исследованы ДНК на предмет наличия мутаций ΔF508 и дополнительно G542Х, S549N, G551D, R553Х и W1282X. Полученные результаты показали наличие мутации ΔF508 у 4 обследуемых из группы ХОЗЛ, что составляет 6%. Частота мутаций в группе необструктивных заболеваний легких составила менее 1:35 (1:70 по хромосомному набору), что соответствует литературным данным. Представленные данные соответствуют гипотезе о том, что гетерозиготность по патогенной мутации муковисцидоза играет определенную роль в патогенезе ХОЗЛ.

The purpose of this study was investigation of the prevalence of ΔF508 mutation of the cystic fibrosis gene in patients with COPD. 66 patients with COPD, 35 ones with nonobstructive pulmonary diseases and 35 healthy volunteers were examined aged of 17—76 years.DNK of the subjects were analysed to reveal mutations ΔF508 and G542Х, S549N, G551D, R553Х, and W1282 additionally. The obtained results show the presence of ΔF508 mutation in 4 patients of COPD group, that is 6% of the number of the latter. The frequency of mutations in the nonobstructive diseases group was less then 1:35 (1:70 for the total number of chromosomes), that is in account with literature data. The present data correspond to the hypothesis about the heterozygosity on pathogenic mutation of cystic fibrosis plays the certain role in COPD pathogenesis.

ReferencesБаранов В., Горбунова В., Иващенко Т. и др. Молекулярный анализ гена и пренатальная диагностика муковисцидоза / / Пульмонология.— 1992.— No 4, Приложение.— С.842.Баранов В., Горбунова В., Иващенко Т. и др. Молекулярный анализ гена и пренатальная диагностика муковисцидоза / / Пульмонология.— 1992.— No 4, Приложение.— С.842.Гембицкая Т.Е., Воронина О.В., Куприна Е.А., Ш епелев А.В. Клинические проявления муковисцидоза и их молекулярно-генетическая характеристика / / Всесоюзный конгресс по болезням органов дыхания, 2-й.— Челябинск, 1991.— С.217.Гембицкая Т.Е., Воронина О.В., Куприна Е.А., Ш епелев А.В. Клинические проявления муковисцидоза и их молекулярно-генетическая характеристика / / Всесоюзный конгресс по болезням органов дыхания, 2-й.— Челябинск, 1991.— С.217.Самильчук Е.И., Лапин Б.А. Наследственный дефицит ai-антитрипсина: клинические проявления, методы диагностики, перспективы лечения / / Тер. арх.— 1988.— No 7 .— С. 141 — 144.Самильчук Е.И., Лапин Б.А. Наследственный дефицит ai-антитрипсина: клинические проявления, методы диагностики, перспективы лечения / / Тер. арх.— 1988.— No 7 .— С. 141 — 144.Чучалин А.Г., Самильчук Е.И. Муковисцидоз: состояние проблемы / / Там же.— 1993.— No 3,— С.З—9.Чучалин А.Г., Самильчук Е.И. Муковисцидоз: состояние проблемы / / Там же.— 1993.— No 3,— С.З—9.Augarten А., Кегет В.-S., Yahav Y. et al. Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849+10 kb C—T mutation / / Lancet.— 1993.— Vol.342.— P.25.Augarten А., Кегет В.-S., Yahav Y. et al. Mild cystic fibrosis and normal or borderline sweat test in patients with the 3849+10 kb C—T mutation / / Lancet.— 1993.— Vol.342.— P.25.Baranov V S., Ivaschenko T.E., Gorbunova V.N. et al. Frequency of the F508 deletion in cystic fibrosis patients from the European part of the USSR / / Hum. G enet.— 1991.— Vol.87.— P .61—64.Baranov V S., Ivaschenko T.E., Gorbunova V.N. et al. Frequency of the F508 deletion in cystic fibrosis patients from the European part of the USSR / / Hum. G enet.— 1991.— Vol.87.— P .61—64.Baranov VS. Molecular diagnosis of some common genetic diseases in Russia and the former USSR: present and future / / J. Med. Genet.— 1993.— Vol.30.— P.141—146.Baranov VS. Molecular diagnosis of some common genetic diseases in Russia and the former USSR: present and future / / J. Med. Genet.— 1993.— Vol.30.— P.141—146.Crystal R.G., Brantly M.L., Hubbard R.C. et al. The alpha-1-antitrypsin gene and its mutations, clinical consequences and strategies for therapy / / Chest.— 1989.— Vol.95.— P .196—208.Crystal R.G., Brantly M.L., Hubbard R.C. et al. The alpha-1-antitrypsin gene and its mutations, clinical consequences and strategies for therapy / / Chest.— 1989.— Vol.95.— P .196—208.Davis P.B., Vargo K. Pulmonary abnormalities in obligate heterozygotes for cystic fibrosis / / Thorax.— 1987.— Vol.42.— P. 120— 125.Davis P.B., Vargo K. Pulmonary abnormalities in obligate heterozygotes for cystic fibrosis / / Thorax.— 1987.— Vol.42.— P. 120— 125.Dean M., Santis G. Heterogeneity in the severity of cystic fibrosis and the role of CFTR gene mutations / / Hum. Genet.— 1994.— Vol.93.— P.364—368.Dean M., Santis G. Heterogeneity in the severity of cystic fibrosis and the role of CFTR gene mutations / / Hum. Genet.— 1994.— Vol.93.— P.364—368.Dumar V, Lafitte Gervais R. et al. Abnormal distribution of cystic fibrosis AF508 allele in adults with chronic bronchial hypersecretion / / Lancet.— 1990.— Vol.335.— P. 1340.Dumar V, Lafitte Gervais R. et al. Abnormal distribution of cystic fibrosis AF508 allele in adults with chronic bronchial hypersecretion / / Lancet.— 1990.— Vol.335.— P. 1340.Gasparini P., Savoia A., Luisetti M. et al. The cystic fibrosis gene is not likely to be involved in chronic obstructive pulmonary disease / / Am. J. Respir. Cell. Mol. Biol.— 1990.— Vol.2.— P .297—299.Gasparini P., Savoia A., Luisetti M. et al. The cystic fibrosis gene is not likely to be involved in chronic obstructive pulmonary disease / / Am. J. Respir. Cell. Mol. Biol.— 1990.— Vol.2.— P .297—299.Hamosh A., Macek M., Nash E. et al. Mutation analysis in cystic fibrosis patients wiih pancreatic sufficiency, pancreatitis, borderline sweat chloride concentrations or isolated congenital bilateral absence of the vas deferens / / Am. J. Hum. Genet.— 1993.— Vol.53.— P.A—1169.Hamosh A., Macek M., Nash E. et al. Mutation analysis in cystic fibrosis patients wiih pancreatic sufficiency, pancreatitis, borderline sweat chloride concentrations or isolated congenital bilateral absence of the vas deferens / / Am. J. Hum. Genet.— 1993.— Vol.53.— P.A—1169.Highsmith W.E., Burch L.H., Boat T.F. et al. Indentification of homozygous point mutation in intron 19 in an inbred CF patent with mild disease and normal sweat chloride: creation of an alternative splice site resulting in CFTR coding region between exon 19 and 20 / / Pediatr. Pulmonoi.— 1991.— Suppl.6.— P.A—22.Highsmith W.E., Burch L.H., Boat T.F. et al. Indentification of homozygous point mutation in intron 19 in an inbred CF patent with mild disease and normal sweat chloride: creation of an alternative splice site resulting in CFTR coding region between exon 19 and 20 / / Pediatr. Pulmonoi.— 1991.— Suppl.6.— P.A—22.Ivaschenko T.E., Baranov VS., Dean M. Two new mutations detected by singlestrand conformation polymorphism analysis in cystic fibrosis from Russia / / Hum. G enet.— 1993.— Vol.91.— P.63—65.Ivaschenko T.E., Baranov VS., Dean M. Two new mutations detected by singlestrand conformation polymorphism analysis in cystic fibrosis from Russia / / Hum. G enet.— 1993.— Vol.91.— P.63—65.Kalinin V.N., Trubnikova I.S., Barbova N.I., Kapranov N.I. AF508 mutation in cystic fibrosis in Moscow region / / European Cystic Fibrosis Conference, 17-th: Abstracts.— Copenhagen, 1991.— P.A-73.Kalinin V.N., Trubnikova I.S., Barbova N.I., Kapranov N.I. AF508 mutation in cystic fibrosis in Moscow region / / European Cystic Fibrosis Conference, 17-th: Abstracts.— Copenhagen, 1991.— P.A-73.Kerem В.-S., Rommens J.M., Buchanan J.A. et al. Identification of the cystic fibrosis gene: genetic analysis / / Science.— 1989.— Vol.245.— P .1073—1080; 1437.Kerem В.-S., Rommens J.M., Buchanan J.A. et al. Identification of the cystic fibrosis gene: genetic analysis / / Science.— 1989.— Vol.245.— P .1073—1080; 1437.Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells / / Nucl. Acid Res.— 1988.— Vol.16.— P.1215.Miller S.A., Dykes D.D., Polesky H.F. A simple salting out procedure for extracting DNA from human nucleated cells / / Nucl. Acid Res.— 1988.— Vol.16.— P.1215.Ng I S.L., Pace R., Richard M.V. et al. Methods for analysis of multiple cystic fibrosis mutations / / Hum. Genet.— 1991.— Vol.87.— P .613—617.Ng I S.L., Pace R., Richard M.V. et al. Methods for analysis of multiple cystic fibrosis mutations / / Hum. Genet.— 1991.— Vol.87.— P .613—617.Pignatti P.F., Bombieri C., Marigo C. et al. Cystic fibrosis mutations found in chronic obstructive pulmonary disease patients / / Am. J. Hum. Genet.— 1993,— Vol.53.— P.A— 1213.Pignatti P.F., Bombieri C., Marigo C. et al. Cystic fibrosis mutations found in chronic obstructive pulmonary disease patients / / Am. J. Hum. Genet.— 1993,— Vol.53.— P.A— 1213.Poller IV, Faber I.P., Scholz S. et al. Sequence analysis of the cystic fibrosis gene in patients with disseminated bronchiectatic lung disease. Application in identification of a cystic fibrosis patient with atypical clinical course / / Klin. W ochenschr.— 1991.— Bd 69.— S .657—663.Poller IV, Faber I.P., Scholz S. et al. Sequence analysis of the cystic fibrosis gene in patients with disseminated bronchiectatic lung disease. Application in identification of a cystic fibrosis patient with atypical clinical course / / Klin. W ochenschr.— 1991.— Bd 69.— S .657—663.Riordan J.R., Rommens J.M., Kerem B.-S. et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA / / Science.— 1989.— Vol.245.— P. 1066—1073.Riordan J.R., Rommens J.M., Kerem B.-S. et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA / / Science.— 1989.— Vol.245.— P. 1066—1073.Rommens J.M., Iannuzzi M.C., Kerem B.-C. et al. Identification of the cystic fibrosis gene: chromosome walking and jumping / / Science.— 1989.— Vol.245,— Р. 59—1065.Rommens J.M., Iannuzzi M.C., Kerem B.-C. et al. Identification of the cystic fibrosis gene: chromosome walking and jumping / / Science.— 1989.— Vol.245,— Р. 59—1065.Strong T.V., Smit L.S., Turpin S.V.. et al. Cystic fibrosis gene mutation in two sisters with mild disease and normal sweat electrolyte levels / / N. Engl. J. M ed.— 1991.— Vol.325.— P .1630— 1634.Strong T.V., Smit L.S., Turpin S.V.. et al. Cystic fibrosis gene mutation in two sisters with mild disease and normal sweat electrolyte levels / / N. Engl. J. M ed.— 1991.— Vol.325.— P .1630— 1634.Tsui L.C. The spectrum of cystic fibrosis mutations / / Trends Genet.— 1992.— Vol.8.— P .392—398.Tsui L.C. The spectrum of cystic fibrosis mutations / / Trends Genet.— 1992.— Vol.8.— P .392—398.Verlinque C., Mercier B., Audrezet M.P. et al. Screening for CFTR gene mutations in Russian patients / / Am. J. Hum. Genet.— 1992.— Vol.51.— P.A— 1361.Verlinque C., Mercier B., Audrezet M.P. et al. Screening for CFTR gene mutations in Russian patients / / Am. J. Hum. Genet.— 1992.— Vol.51.— P.A— 1361.Verlinque C., Audrezet M.P., Savov A. et al. Complete screening for CFTR gene mutations in three samples of CF patients from Eastern Europe / / Ibid.— 1993.— Vol.53.— P.A—873.Verlinque C., Audrezet M.P., Savov A. et al. Complete screening for CFTR gene mutations in three samples of CF patients from Eastern Europe / / Ibid.— 1993.— Vol.53.— P.A—873.Voronina O., Gaitskhoki V, Potapova O. et al. Correlation of F508 deletion with CF clinical form / / European Cystic Fibrosis Conference, 17-th: Abstracts.— Copenhagen, 1991.— P.A—76.Voronina O., Gaitskhoki V, Potapova O. et al. Correlation of F508 deletion with CF clinical form / / European Cystic Fibrosis Conference, 17-th: Abstracts.— Copenhagen, 1991.— P.A—76.Walsh P.C., Metzger D.A., Higuchi R. Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material / / Bio Techniques.— 1991.— Vol. 10.— P.506—513.Walsh P.C., Metzger D.A., Higuchi R. Chelex 100 as a medium for simple extraction of DNA for PCR-based typing from forensic material / / Bio Techniques.— 1991.— Vol. 10.— P.506—513.Zielenski J., Rozmahel R., Bozon D. et al. Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene / / Genomics.— 1991.— Vol. 10.— P.214—228.Zielenski J., Rozmahel R., Bozon D. et al. Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene / / Genomics.— 1991.— Vol. 10.— P.214—228.

The authors declare that there are no conflicts of interest present.