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Abstract
FEATURES OF CYSTIC FIBROSIS COURSE IN CHILDREN DEPENDING ON INTERLEUKIN-4 GENE MUTATION
Drobova N. M.
Cystic fibrosis (CF) course features depend not only on the difference in CF transmembrane conductance regulator gene mutations, but also on other gene modifiers. Interleukin-4 (IL-4) gene is a one of gene modifiers. The aim of the present study was to improve medical care for patients with CF by clarifying the pathogenic role of IL-4 gene polymorphism in the course of the disease. The study involved examination of 42 children with CF and 54 practically healthy children as control group. Patient examination was carried out by the standard methods in the remission period. Determination of C589T polymorphism of IL-4 gene was carried out using polymerase chain reaction in real time. DNA was isolated from buccal epithelium cells. Patients with IL-4 gene mutation (C589T) were characterized by more frequent primary manifestation of the respiratory signs, Staphylococcus aureus predominance within respiratory pathological microorganisms, the incidences of bronchiectasis and lung fibrosis, more severe liver lesions, elevated total serum immunoglobulin E level, elevated levels of the CD25 lymphocytes, circulating immune complex and reduced immunoglobulin A levels. The data demonstrate features of CF phenotype associated with IL-4 gene polymorphism.
Key words: children, cystic fibrosis, clinical and paraclinical features, interleukin-4 gene mutation.
ОСОБЛИВОСТІ ПЕРЕБІГУ МУКОВІСЦИДОЗУ У ДІТЕЙ ЗАЛЕЖНО ВІД МУТАЦІЇ ГЕНУ ІНТЕРЛЕЙКІНУ-4
Дробова Н.М.
Перебіг муковісцидозу (МВ) залежить не тільки від мутації гену трансмембранного регулятора МВ, але й від інших генів-модифікаторів. Одним з таких факторів виступає ген інтерлейкіну-4 (ІЛ-4). Метою дослідження стало удосконалення медичної допомоги хворим на МВ шляхом уточнення патогенетичної ролі поліморфізму гену-модифікатора запалення ІЛ-4 у перебігу хвороби. Під спостереженням знаходилося 42 дитини з діагнозом МВ. Контрольну групу склали 54 практично здорових дітей, рандомізованих за віком. Обстеження пацієнтів проводилося згідно стандартних методик. Визначення поліморфізму C589T гена IL-4 проводили з використанням полімеразної ланцюгової реакції в реальному часі. ДНК виділяли з клітин букального епітелію. Для хворих на МВ з мутацією гену ІЛ-4 С589Т характерно більш часта маніфестація легеневих проявів, вища частота зустрічаємості бронхоектазів та пневмофіброзу легенів, циротичних змін паренхіми печінки, переважання Staphylococcus aureus у бактеріальному пейзажі мокротиння, підвищення загального імуноглобуліну E, лімфоцитів CD25, циркулюючих імунних комплексів та зниження імуноглобуліну A. Охарактеризовано фенотип МВ залежно від наявності мутації гену-модифікатору запалення ІЛ-4.
Ключові слова: діти, муковісцидоз, клініко-параклінічні особливості, мутація гену інтерлейкіну-4.
ОСОБЕННОСТИ ТЕЧЕНИЯ МУКОВИСЦИДОЗА У ДЕТЕЙ В ЗАВИСИМОСТИ ОТ МУТАЦИИ ГЕНА ИНТЕРЛЕЙКИНА-4
Дробова Н.М.
Течение муковисцидоза (МВ) зависит не только от мутации гена трансмембранного регулятора МВ, но и от других генов-модификаторов. Одним из таких факторов выступает ген интерлейкина-4 (ИЛ-4). Целью исследования явилось усовершенствование медицинской помощи больным МВ путем уточнения патогенетической роли полиморфизма гена-модификатора воспаления ИЛ-4 в течении болезни. Под наблюдением находилось 42 ребенка с диагнозом МВ. Контрольную группу составили 54 практически здоровых ребенка, рандомизированных по возрасту. Обследование пациентов проводилось согласно стандартных методик. Определение полиморфизма C589T гена IL-4 проводили с использованием полимеразной цепной реакции в реальном времени. ДНК выделяли из клеток буккального эпителия. Для генотипа ИЛ-4 с мутацией С589Т у больных МВ характерно более частая манифестация легочных проявлений, высокая частота встречаемости бронхоэктазов и пневмофиброза легких, цирротических изменений паренхимы печени, преобладание Staphylococcus aureus в бактериальном пейзаже мокроти, повышение общего иммуноглобулина E, CD25, циркулирующих иммунных комплексов и снижение иммуноглобулина A. Охарактеризованы фенотип МВ в зависимости от наличия мутации гена-модификатора воспаления ИЛ-4.
Ключевые слова: дети, муковисцидоз, клинико-параклинические особенности, мутация гена интерлейкина-4.
References
Accurso, F. J., Marci K. Sontag, M. K. (2008). Gene modifiers in cystic fibrosis. Journal of Clinical Investigation, 118(3), 839-841. doi:10.1172/JCI35138
Bhagirath, A.Y., Li, Y., Somayajula, D. (2016). Cystic fibrosis lung environment and Pseudomonas aeruginosa infection. BMC Pulmonary Medicine, 16, 174. doi:10.1186/s12890-016-0339-5
Bombieri, C., Seia, M., Castellani, C. (2015). Genotypes and Phenotypes in Cystic Fibrosis and Cystic Fibrosis Transmembrane Regulator– Related Disorders. Seminars in Respiratory and Critical Care Medicine, 36, 180–193. doi: 10.1055/s-0035-1547318
Buranawut, K., Boyle, M.P., Cheng, S., Steiner, L.L., McDougal, K., Fallin, M.D., Merlo, C., Zeitlin, P.L., Rosenstein, B.J., Mogayzel Jr., P.J., Wang, X., Cutting, G.R. (2007). Variants in mannose-binding lectin and tumour necrosis factor alpha affect survival incystic fibrosis. Journal of Medical Genetics, 44, 209–14. doi: 10.1136/jmg.2006.046318
Chalmers, J.D., Fleming, G.B., Hill, A.T., Kilpatrick, D.C. (2011). Impact of mannose-binding lectininsufficiency on the course of cystic fibrosis: a review and meta-analysis. Glycobiology, 21, 271–82.
doi.org/10.1093/glycob/cwq161
Cutting, G.R. (2010). Modifier genes in Mendelian disorders: the example of cystic fibrosis. Annals of the New York Academy of Sciences, 1214, 57-69. doi: 10.1111/j.1749-6632.2010.05879.x.
De Vries, L., Griffiths, A., Armstrong, D., Robinson, P.J. (2014). Cytokine gene polymorphisms and severity of CF lung disease. Journal of Cystic Fibrosis, 13(6), 699-705. doi: 10.1016/j.jcf.2014.04.007
Dorfman, R. (2012). Modifier gene studies to identify new therapeutic targets in cystic fibrosis. Current Pharmaceutical Design, 18, 674–82. doi: 10.2174/138161212799315920
Döring, G., Flume, P., Heijerman, H. (2012). Treatment of lung infection in patients with cystic fibrosis: current and future strategies. Journal of Cystic Fibrosis, 11 (6), 461-479. doi:
1016/j.jcf.2012.10.004
Flume, P.A., Mogayzel, P.J.Jr, Robinson, K.A., Goss, C.H., Rosenblatt, R.L., Kuhn, R.J., Marshall, B.C. (2009). Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. American Journal of Respiratory and Critical Care Medicine, 180(9), 802-808. doi: 10.1164/rccm.200812-1845pp
Gembitskaya, T.E., Kelembet, N.A., Ivaschenko, T.E. (2006). Znachenie nekotoryih genov-modifikatorov v klinicheskom techenii i ishodah mukovistsidoza. [The significance of some modifier genes in the clinical course and outcome of cystic fibrosis]. Pulmonologiya, 1, 57–60.
Golimbet, V.E., Volel, B.A., Korovaitseva, G.I., Kasparov, S.V., Kondratiev, N.V., Kopylov, F.Yu. (2017). Assotsiatsiya vospalitelnyih genov s nevrotizmom, trevozhnostyu i depressiey u muzhchin s ishemicheskoy boleznyu serdtsa. [Association of inflammatory genes with neuroticism, anxiety and depression in male patients with coronary heart disease]. Zhurnal nevrologii i psihiatrii, 117 (3), 74-79. doi: 10.17116 / jnevro20171173174-79
Guillot, L., Beucher, J., Tabary, O., Le Rouzic, P., Clement, A., Corvol, H. (2014). Lung disease modifier genes in cystic fibrosis. The International Journal of Biochemistry & Cell Biology, 52, 83-93. doi: 10.1016/j.biocel.2014.02.011.
Kapranov, N.I., Kashirskaya, N.Yu. (2014). Mucoviscidoz. [Cystic Fibrosis]. Moskva: Medpraktika.
Kostina, E.M., Molotilov, B.A., Levashova, O.A., Osipova, M.V. (2013). Izuchenie polimorfizma genov tsitokinov IL-4, IL-10, IL-17A i TNF-α u bolnyih s infektsionnozavisimoy bronhialnoy astmoy. [The study of polymorphism of cytokine genes IL-4, IL-10, IL-17A and TNF-α in patients with infectious dependent bronchial asthma]. Immunopatologiya, allergologiya, infektologiya, 1, 53-58.
O'Neal, W.K., Knowles, M.R. (2018). Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease. Annual Review of Genomics and Human Genetics, 19. doi: 10.1146/annurev-genom-083117-021329
Rosenwasser, L.J. (1999). Promoter polymorphism in the candidate genes, IL-4, IL-9, TGF-beta1, for atopy and asthma. International Archives of Allergy and Immunology, 118(2-4), 268-70.
Rosenwasser, L.J, Klemm, .J., Dresback, J.K., Inamura, H., Mascali, J.J., Klinnert, M., Borish, L. (1995). Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clinical & Experimental Allergy, 2, 74-8.
Sergienko, D. F. (2011). Kliniko-patogeneticheskoe znachenie geneticheskih modifikatsiy i narusheniya immunoregulyatornyih mehanizmov u detey s mukovistsidozom. [Clinical-Pathogenetic Importance of Genetic Modifications and Infringement of Immunoregulatory Mechanisms in Children with Cystic Fibrosis]. (Avtoreferat dissertatsii na soiskanie uchenoy stepeni doktora meditsinskih nauk). Astrahanskaya gosudarstvennaya meditsinskaya akademiya Federalnogo agentstva po zdravoohraneniyu i sotsialnomu razvitiyu, Astrahan.
Weiler, C.A., Drumm, M.L. (2013). Genetic influences on cystic fibrosis lung disease severity. Frontiers in Pharmacology, 4, 40. doi: 10.3389/fphar.2013.00040
Yarden, J., Radojkovic, D., De Boeck, K., Macek, Jr M, Zemkova, D., Vavrova, V., Vlietinck J., Cassiman, J-J., Cuppens, H. (2005). Association of tumour necrosis factor alpha variants with the CF pulmonary phenotype. Thorax, 60, 320–5. doi: 10.1136/thx.2004.025262
Yokoyama, E., Chávez-Saldana, M., Orozco, L., Cuevas, F., Lezana, J.L., Vigueras-Villasenor, R.M., Rojas-Castaneda, J.C., Landero, D.A. (2018). Influence of SNPs in Genes that Modulate Lung Disease Severity in a Group of Mexican Patients with Cystic Fibrosis. Archives of Medical Research, 0188-4409 (18), 30110-3. doi: 10.1016/j.arcmed.2018.04.010
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