Цель: изучить ассоциацию однонуклеотидного полиморфизма rs6737848 гена SOCS5 с аллергической бронхиальной астмой (БА). Материалы и методы. Обследовано 59 пациентов (19 мужчин и 40 женщин) с аллергической БА и 50 здоровых лиц (29 мужчин и 21 женщина), составивших контрольную группу. Всем пациентам проведено клинико-инструментальное и лабораторное обследования на базе Красноярской межрайонной клинической больницы №20 им. И.С. Берзона и молекулярно-генетическое исследование на базах Российско-итальянской лаборатории медицинской генетики «MAGI» и лаборатории молекулярно-генетических исследований терапевтических заболеваний НИИТПМ – филиал ИЦиГ СО РАН (Новосибирск). Статистическая обработка материала осуществлялась с использованием программы Statistica for Windows 7.0. Результаты. По результатам исследования выявлено, что частота носителей гомозиготного генотипа СC гена SOCS5 по распространенному аллелю среди больных с аллергической БА была статистически значимо выше по сравнению с контрольной группой. Заключение. Гомозиготный генотип СС гена SOCS5 является фактором риска развития аллергической БА.
Aim: to study the association of mononucleotide polymorphism rs6737848 SOCS5 gene with the risk of development of allergic bronchial asthma. Material and methods. Totally 59 patients studied (19 males, 40 females) with allergic bronchial asthma and 50 healthy people (29 males, 21 females) of controls. All patients underwent clinical and instrumental and laboratory investigations in KICH №20 (Krasnoyarsk city) and molecular-genetic investigation of DNA in the Russia-Italian laboratory “MAGI” (Krasnoyarsk city) and Institution of Internal and Preventive Medicine (Novosibirsk city). Statistics included standard programs: Statistica for Windows 7.0. Results. The results of the study showed statistical predominance of prevalent genotype СС of SOCS5 gene in allergic bronchial asthma patients, comparing to control group.
Conclusion. Homozygous genotype of СС gene of SOCS5 is a risk factor for allergic bronchial asthma.
Global Initiative for Asthma. Global strategy for asthma management and prevention. 2016 [Accessed 2016]. Available on [www.ginasthma.org].
2. March ME, Sleiman PM, Hakonarson H. The genetics of asthma and allergic disorders. Discovery Medicine. 2011;(56)11:35-45. https://doi.org/10. 1016/b978-0-12-383834-6.00063-x
3. Чучалин А.Г. Бронхиальная астма. М.: Медицина, 2003:160 с. [Chuchalin AG. Bronchial asthma. Moscow: Medicine, 2003:160 p. (In Russ.)].
4. Чучалин А.Г., Илькович М.М. Справочник по пульмонологии. М.: ГЭОТАР-Медиа, 2014:928 с. [Chuchalin AG, Ilkovich MM. Handbook of pulmonology. Moscow: GEOTAR-Media, 2014:928 p. (In Russ.)].
5. Grinshtein YI, Shestovitsky VA, Maksimova AV, Topolskaya NV, Aristov AI, Cherkashina II. The cytology and chemiluminescence of phagocytes in bronchoalveolar lavage fluid from elderly patients with bronchial asthma. Adv Gerontol. 2014;4(2):119-22. https://doi.org/10.1134/s2079057014020076
6. Салтыкова И.В., Фрейдин М.Б., Брагина Е.Ю., Огородова Л.М., Пузырев В.П. Ассоциация полиморфизма rs6737848 гена SOCS5 с бронхиальной астмой. Вестник Российской академии медицинских наук. 2013;(7):53-6 [Saltykova IV, Freidin MB, Bragina EIu, Ogorodova LM, Puzyrev VP. Association of polymorphism Rs6737848 in the Socs5 gene with bronchial asthma. Vestn Ross Akad Med Nauk. 2013;(7):53-6 (In Russ.)]. https://doi.org/10.15690/ vramn.v68i7.713
7. Фрейдин М.Б., Огородова Л.М., Цой А.Н., Бердникова Н.Г. Генетика бронхиальной астмы. Генетика бронхолегочных заболеваний. М.: Издательский холдинг «Атмосфера», 2010:78-104 [Freidin MB, Ogorodova LM, Coy AN, Berdnikova NG. Genetics of asthma. Genetics of bronchopulmonary diseases. Moscow: Atmosphere, 2010:78-104 (In Russ.)].
8. Cherkashina II, Nikulina SI, Logvinenko NI, Voevoda MI, Maksimov VN, Liberdovskaia ED. The specific features of TNF-alpha gene polymorphism in asthmatic patients and their relatives. Probl Tuberk Bolezn Legk. 2009;(8):51-6.
9. Cherkashina II, Nikulina SI, Logvinenko NI, Maksimov VN, Liberdovskaia ED. Clinical and genetic features in patients with asthma and their relatives. Probl Tuberk Bolezn Legk. 2008;(9):47-50.
10. Vercelli D. Discovering susceptibility genes for asthma and allergy. Nature Reviews Immunology. 2008;8(3):169-82. https://doi.org/ 10.1038/nri2257
11. Hilton DJ. Negative regulators of cytokine signal transduction. Cellular and Molecular Life Sciences. 1999;55:1568-77. https://doi.org/ 10.1007/s000180 050396
12. Naka T, Fujimoto M, Kishimoto T. Negative regulation of cytokine signaling: STAT-induced STAT inhibitor. Trends in Biochemical Sciences. 1999;24:394-8. https://doi.org/10.1016/s0968-0004(99)01454-1
13. Yasukawa H, Sasaki A, Yoshimura A. Negative regulation of cytokine signaling pathways. Аnnual Review of Immunology. 2000;18:143-64. https://doi.org/10.1146/annurev.immunol.18.1.143
14. Feng ZP, Chandrashekaran IR, Low A, Speed TP, Nicholson SE, Norton RS. The N-terminal domains of SOCS proteins: a conserved region in the disordered N-termini of SOCS4 and 5. Proteins. 2012;80(3):946-57. https://doi. org/10.1002/prot.23252
15. Seki Y, Hayashi K, Matsumoto A, Seki N, Tsukada J, Ransom J, Naka T, Kishimoto T, Yoshimura A, Kubo M. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proceedings of the National Academy of Sciences of the USA. 2002;99(20):13003-8. https://doi.org/10.1073/pnas.202477099
16. Saltykova IV, Ogorodova LM, Bragina EY, Puzyrev VP, Freidin MB. Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma. Acta Tropica. 2014;139:53-6. https://doi. org/10.1016/j.actatropica.2014.07.004
________________________________________________
1. Global Initiative for Asthma. Global strategy for asthma management and prevention. 2016 [Accessed 2016]. Available on [www.ginasthma.org].
2. March ME, Sleiman PM, Hakonarson H. The genetics of asthma and allergic disorders. Discovery Medicine. 2011;(56)11:35-45. https://doi.org/10. 1016/b978-0-12-383834-6.00063-x
3. Chuchalin AG. Bronchial asthma. Moscow: Medicine, 2003:160 p. (In Russ.).
4.Chuchalin AG, Ilkovich MM. Handbook of pulmonology. Moscow: GEOTAR-Media, 2014:928 p. (In Russ.).
5. Grinshtein YI, Shestovitsky VA, Maksimova AV, Topolskaya NV, Aristov AI, Cherkashina II. The cytology and chemiluminescence of phagocytes in bronchoalveolar lavage fluid from elderly patients with bronchial asthma. Adv Gerontol. 2014;4(2):119-22. https://doi.org/10.1134/s2079057014020076
6. Saltykova IV, Freidin MB, Bragina EIu, Ogorodova LM, Puzyrev VP. Association of polymorphism Rs6737848 in the Socs5 gene with bronchial asthma. Vestn Ross Akad Med Nauk. 2013;(7):53-6 (In Russ.). https://doi.org/10.15690/ vramn.v68i7.713
7. Freidin MB, Ogorodova LM, Coy AN, Berdnikova NG. Genetics of asthma. Genetics of bronchopulmonary diseases. Moscow: Atmosphere, 2010:78-104 (In Russ.).
8. Cherkashina II, Nikulina SI, Logvinenko NI, Voevoda MI, Maksimov VN, Liberdovskaia ED. The specific features of TNF-alpha gene polymorphism in asthmatic patients and their relatives. Probl Tuberk Bolezn Legk. 2009;(8):51-6.
9. Cherkashina II, Nikulina SI, Logvinenko NI, Maksimov VN, Liberdovskaia ED. Clinical and genetic features in patients with asthma and their relatives. Probl Tuberk Bolezn Legk. 2008;(9):47-50.
10. Vercelli D. Discovering susceptibility genes for asthma and allergy. Nature Reviews Immunology. 2008;8(3):169-82. https://doi.org/ 10.1038/nri2257
11. Hilton DJ. Negative regulators of cytokine signal transduction. Cellular and Molecular Life Sciences. 1999;55:1568-77. https://doi.org/ 10.1007/s000180 050396
12. Naka T, Fujimoto M, Kishimoto T. Negative regulation of cytokine signaling: STAT-induced STAT inhibitor. Trends in Biochemical Sciences. 1999;24:394-8. https://doi.org/10.1016/s0968-0004(99)01454-1
13. Yasukawa H, Sasaki A, Yoshimura A. Negative regulation of cytokine signaling pathways. Аnnual Review of Immunology. 2000;18:143-64. https://doi.org/10.1146/annurev.immunol.18.1.143
14. Feng ZP, Chandrashekaran IR, Low A, Speed TP, Nicholson SE, Norton RS. The N-terminal domains of SOCS proteins: a conserved region in the disordered N-termini of SOCS4 and 5. Proteins. 2012;80(3):946-57. https://doi. org/10.1002/prot.23252
15. Seki Y, Hayashi K, Matsumoto A, Seki N, Tsukada J, Ransom J, Naka T, Kishimoto T, Yoshimura A, Kubo M. Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation. Proceedings of the National Academy of Sciences of the USA. 2002;99(20):13003-8. https://doi.org/10.1073/pnas.202477099
16. Saltykova IV, Ogorodova LM, Bragina EY, Puzyrev VP, Freidin MB. Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma. Acta Tropica. 2014;139:53-6. https://doi. org/10.1016/j.actatropica.2014.07.004
1 ФГБОУ ВО «Красноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого» Минздрава России, Красноярск, Россия;
2 Научно-исследовательский институт терапии и профилактической медицины – филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» (НИИТПМ – филиал ИЦиГ СО РАН), Новосибирск, Россия;
3 ФГБОУ ВО «Красноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого» Минздрава России, Красноярск, Россия
1 Krasnoyarsk State Medical University named after of professor V.F. Voino-Yasenetsky of the Ministry of Health of the Russian Federation, Department of internal diseases №1, Krasnoyarsk, Russia;
2 Research Institutе of Internal and Preventive Medicine – Branch of the Federal Research Center Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia;
3 Prof. V.F. Voino-Yasenetski Krasnoyarsk State Medical University of the Ministry of Health of the Russian Federation, Department of Therapy, Krasnoyarsk, Russia