cfpdБюллетень физиологии и патологии дыханияBulletin Physiology and Pathology of Respiration1998-5029Дальневосточный научный центр физиологии и патологии дыхания10.12737/article_5c88b6c40f6135.99480729cfpd-186Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHПОЛИМОРФИЗМ ГЕНА TRPM8 КАК НЕЗАВИСИМЫЙ ФАКТОР ФОРМИРОВАНИЯ БРОНХИАЛЬНОЙ ОБСТРУКЦИИ У БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙPOLYMORPHISM OF TRPM8 GENE AS AN INDEPENDENT FACTOR OF BRONCHIAL OBSUCTION IN ASTHMAНаумовД. Е.NaumovD. E.denn1985@bk.ruГассанД. А.GassanD. A.dncfpd@dncfpd.ruКотоваО. О.KotovaO. O.dncfpd@dncfpd.ruПриходькоА. Г.PrikhodkoA. G.prih-anya@ya.ruПерельманЮ. М.PerelmanJ. M.jperelman@mail.ruКолосовВ. П.KolosovV. P.dncfpd@dncfpd.ruФедеральное государственное бюджетное научное учреждение «Дальневосточный научный центр физиологии и патологии дыхания»Far Eastern Scientific Center of Physiology and Pathology of Respiration2019181120190713136Copyright © Наумов Д.Е., Гассан Д.А., Котова О.О., Приходько А.Г., Перельман Ю.М., Колосов В.П., 20192019Наумов Д.Е., Гассан Д.А., Котова О.О., Приходько А.Г., Перельман Ю.М., Колосов В.П.Naumov D.E., Gassan D.A., Kotova O.O., Prikhodko A.G., Perelman J.M., Kolosov V.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cfpd.elpub.ru/jour/article/view/186

Наряду с хронической обструктивной болезнью легких, бронхиальная астма (БА) так же может сопровождаться необратимым снижением функции легких. Известно, что среди прочих причин данного явления, определенную роль может играть генетическая предрасположенность. Целью исследования было изучить эффект полиморфизма rs11562975 гена TRPM8 на функцию легких у больных БА. Обследовано 285 больных неконтролируемой персистирующей БА легкой и средней степени. Всем больным была выполнена стандартная спирометрия исходно и через 15 минут после ингаляции бронхолитика фенотерола. Полиморфизм rs11562975 был генотипирован с помощью LATE-ПЦР. Установлено, что полиморфизм значимо взаимосвязан с рядом параметров функции внешнего дыхания, в том числе индексом Тиффно (ИТ). Носительство генотипов GC и CC сопровождается сниженными значениями как пре-, так и постбронходилатационного ИТ. При этом частота генотипов GС+СC достоверно выше среди больных с ИТ<70% исходно, и среди пациентов с ИТ<80% после действия бронхолитика. Все ассоциации полиморфизма с ИТ значимы независимо от пола, возраста, индекса массы тела, длительности заболевания, возраста начала заболевания, индекса курильщика и холодовой гиперреактивности дыхательных путей. Полученные результаты свидетельствуют о потенциальном наличии TRPM8-зависимого компонента патогенеза БА.

Along with chronic obstructive pulmonary disease, asthma may also be accompanied by an irreversible decrease in lung function. It is known that among other causes of this phenomenon genetic predisposition may play a certain role. The aim of the study was to investigate the effect of rs11562975 polymorphism of TRPM8 gene on lung function in patients with asthma. The study enrolled 285 patients with uncontrolled persistent mild and moderate asthma. All patients underwent standard spirometry before and 15 minutes after inhalation of fenoterol bronchodilator. rs11562975 polymorphism was genotyped using LATE-PCR. It has been established that polymorphism is significantly interrelated with a number of lung function parameters, including FEV1/FVC. Carriage of GC and CC genotypes was accompanied by reduced values of both pre- and postbronchodilator ratio FEV1/FVC. At the same time, the frequency of GС+СC genotypes was significantly higher among patients with baseline FEV1/FVC<70%, and among patients with postbronchodilator FEV1/FVC<80%. All associations of the polymorphism with FEV1/FVC were significant regardless of gender, age, body mass index, duration of the disease, age of asthma onset, pack-year index and cold airway hyperresponsiveness. The obtained results indicate the potential presence of TRPM8-dependent component of asthma pathogenesis

бронхиальная астмахолодовые рецепторыгенетический полиморфизмфункция внешнего дыханиябронхиальная обструкцияTRPM8asthmacold receptorsTRPM8genetic polymorphismlung functionbronchial obstructionReferencesГассан Д.А., Наумов Д.Е., Котова О.О., Приходько А.Г., Колосов В.П. Полиморфизм гена TRPM8 и курение как факторы формирования тяжелой бронхиальной обструкции у больных бронхиальной астмой. Бюллетень физиологии и патологии дыхания 2017. Вып.65. С.24-30. doi: 10.12737/article_59acaae9dad902.64338769Гассан Д.А., Наумов Д.Е., Котова О.О., Приходько А.Г., Колосов В.П. Полиморфизм гена TRPM8 и курение как факторы формирования тяжелой бронхиальной обструкции у больных бронхиальной астмой. Бюллетень физиологии и патологии дыхания 2017. Вып.65. С.24-30. doi: 10.12737/article_59acaae9dad902.64338769Bai T.R., Vonk J.M., Postma D.S., Boezen H.M. Severe exacerbations predict excess lung function decline in asthma // Eur. Respir. J. 2007. Vol.30, №3. 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P.322-327.Vonk J.M., Jongepier H., Panhuysen C.I., Schouten J.P., Bleecker E.R., Postma D.S. Risk factors associated with the presence of irreversible airflow limitation and reduced transfer coefficient in patients with asthma after 26 years of follow up // Thorax. 2003. Vol.58, №4. P.322-327.Gassan D.A., Naumov D.E., Kotova O.O., Prikhodko A.G., Perelman J.M., Kolosov V.P. TRPM8 gene polymorphism and smoking as the factors of severe bronchial obstruction in patients with asthma. Bûlleten' fiziologii i patologii dyhaniâ 2017; 65:24-30 (in Russian). doi: 10.12737/article_59acaae9dad902.64338769Gassan D.A., Naumov D.E., Kotova O.O., Prikhodko A.G., Perelman J.M., Kolosov V.P. TRPM8 gene polymorphism and smoking as the factors of severe bronchial obstruction in patients with asthma. Bûlleten' fiziologii i patologii dyhaniâ 2017; 65:24-30 (in Russian). doi: 10.12737/article_59acaae9dad902.64338769Bai T.R., Vonk J.M., Postma D.S., Boezen H.M. Severe exacerbations predict excess lung function decline in asthma. Eur. Respir. J. 2007; 30(3):452-456.Bai T.R., Vonk J.M., Postma D.S., Boezen H.M. Severe exacerbations predict excess lung function decline in asthma. Eur. Respir. J. 2007; 30(3):452-456.Barton S.J., Koppelman G.H., Vonk J.M., Browning C.A., Nolte I.M., Stewart C.E., Bainbridge S., Mutch S., Rose-Zerilli M.J., Postma D.S., Maniatis N., Henry A.P., Hall I.P., Holgate S.T., Tighe P., Holloway J.W., Sayers I. PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline. J. Allergy Clin. Immunol. 2009; 123(6):1391-1400.Barton S.J., Koppelman G.H., Vonk J.M., Browning C.A., Nolte I.M., Stewart C.E., Bainbridge S., Mutch S., Rose-Zerilli M.J., Postma D.S., Maniatis N., Henry A.P., Hall I.P., Holgate S.T., Tighe P., Holloway J.W., Sayers I. PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline. J. Allergy Clin. Immunol. 2009; 123(6):1391-1400.de Marco R., Marcon A., Jarvis D., Accordini S., Bugiani M., Cazzoletti L., Cerveri I., Corsico A., Gislason D., Gulsvik A., Jõgi R., Martínez-Moratalla J., Pin I., Janson C.; ECRHS Therapy Group. Inhaled steroids are associated with reduced lung function decline in subjects with asthma with elevated total IgE. J. Allergy Clin. Immunol. 2007; 119(3):611-617.de Marco R., Marcon A., Jarvis D., Accordini S., Bugiani M., Cazzoletti L., Cerveri I., Corsico A., Gislason D., Gulsvik A., Jõgi R., Martínez-Moratalla J., Pin I., Janson C.; ECRHS Therapy Group. Inhaled steroids are associated with reduced lung function decline in subjects with asthma with elevated total IgE. J. Allergy Clin. Immunol. 2007; 119(3):611-617.Dijkstra A., Howard T.D., Vonk J.M., Ampleford E.J., Lange L.A., Bleecker E.R., Meyers D.A., Postma D.S.Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma. J. Allergy Clin. Immunol. 2006; 117(3):604-611.Dijkstra A., Howard T.D., Vonk J.M., Ampleford E.J., Lange L.A., Bleecker E.R., Meyers D.A., Postma D.S.Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma. J. Allergy Clin. Immunol. 2006; 117(3):604-611.Dijkstra A., Vonk J.M., Jongepier H., Koppelman G.H., Schouten J.P., ten Hacken N.H., Timens W., Postma D.S. Lung function decline in asthma: association with inhaled corticosteroids, smoking and sex. Thorax 2006; 61(2): 105-110.Dijkstra A., Vonk J.M., Jongepier H., Koppelman G.H., Schouten J.P., ten Hacken N.H., Timens W., Postma D.S. Lung function decline in asthma: association with inhaled corticosteroids, smoking and sex. Thorax 2006; 61(2): 105-110.Fernández J.A., Skryma R., Bidaux G., Magleby K.L., Scholfield C.N., McGeown J.G., Prevarskaya N., Zholos A.V. Short isoforms of the cold receptor TRPM8 inhibit channel gating by mimicking heat action rather than chemical inhibitors. J. Biol. Chem. 2012; 287(5):2963-2970.Fernández J.A., Skryma R., Bidaux G., Magleby K.L., Scholfield C.N., McGeown J.G., Prevarskaya N., Zholos A.V. Short isoforms of the cold receptor TRPM8 inhibit channel gating by mimicking heat action rather than chemical inhibitors. J. Biol. Chem. 2012; 287(5):2963-2970.Fujita T., Liu Y., Higashitsuji H., Itoh K., Shibasaki K., Fujita J., Nishiyama H. Involvement of TRPV3 and TRPM8 ion channel proteins in induction of mammalian cold-inducible proteins. Biochem. Biophys. Res. Commun. 2018; 495(1):935-940.Fujita T., Liu Y., Higashitsuji H., Itoh K., Shibasaki K., Fujita J., Nishiyama H. Involvement of TRPV3 and TRPM8 ion channel proteins in induction of mammalian cold-inducible proteins. Biochem. Biophys. Res. Commun. 2018; 495(1):935-940.Guerra S., Sherrill D.L., Kurzius-Spencer M., Venker C., Halonen M., Quan S.F., Martinez F.D. The course of persistent airflow limitation in subjects with and without asthma. Respir. Med. 2008; 102(10):1473-1482.Guerra S., Sherrill D.L., Kurzius-Spencer M., Venker C., Halonen M., Quan S.F., Martinez F.D. The course of persistent airflow limitation in subjects with and without asthma. Respir. Med. 2008; 102(10):1473-1482.Imboden M., Bouzigon E., Curjuric I., Ramasamy A., Kumar A., Hancock D.B., Wilk J.B., Vonk J.M., Thun G.A., Siroux V., Nadif R.,and other authors Genome-wide association study of lung function decline in adults with and without asthma. J. Allergy Clin. 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The authors declare that there are no conflicts of interest present.