pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2022-32-4-608-615pulmo-4140Research ArticleЛЕКЦИИLECTIONSГенетические механизмы эссенциальной эмфиземы легкихGenetic mechanisms of primary lung emphysemaАмироваТ. О.AmirovaT. O.

Амирова Татьяна Олеговна – врач персонализированной медицины, генетик Клиники «Laboratoires Reunis, Dr. Amirova», член исследовательской группы по изучению системных биологических моделей полигенных заболеваний, аффилированной со Школой системной биологии, Университет Джорджа Мейсона (Фэрфакс, США), руководитель Школы прецизионной метаболомной медицины, Институт PreventAge, член Коалиции персонализированной медицины, преподаватель UniCapital Corp.

119296, Москва, Ленинский просп., 62 / 1

тел.: (495) 347-09-39

Tatyana O. Amirova, Doctor of personalized medicine, geneticist at Laboratoires Reunis, Member of polygenic diseases biological modelling research group, affiliated with School of Systems Biology, George Mason University (Fairfax, USA), Head of Precision Metabolomic Medicine School, PreventAge Institute; Member of Personalized Medicine Coalition, Faculty member of UCPC

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tel.: (495) 347-09-39

dr.amirova2000@gmail.comКлиника “Laboratoires Reunis, Dr. Amirova”comРоссияClinic “Laboratoires Reunis, Dr. Amirova”Russian Federation202217082022324608615Copyright © Амирова Т.О., 20222022Амирова Т.О.Amirova T.O.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/4140

Персонализированный подход к лечению полигенного заболевания, каким является эмфизема легких, предоставляет возможность выбора наиболее эффективных препаратов для каждого отдельного клинического случая. Прогресс в понимании молекулярных механизмов этого заболевания позволяет по-новому взглянуть на классификацию, причины вариабельности фенотипа, прогноз, возможность превентивных мер до развития развернутой клинической картины.

Целью данной работы было собрать воедино имеющиеся данные о вкладе генетических мутаций в развитие эмфиземы легких, охарактеризовать эндотипы, определить направления персонализированного лечения.

Результаты

Результаты. Внимание клиницистов при диагностике эссенциальной эмфиземы сфокусировано на определении в сыворотке крови уровня α1-антитрипсина и мутаций гена SERPINA1 в 3, 4, 5 и 6-м экзонах. Это важная, но не полная информация о причинах и прогнозе течения заболевания. Она не учитывает влияния генов-модификаторов и межгенных взаимодействий. При этом интактный ген SERPINA1 не является гарантом отсутствия предпосылок к развитию эссенциальной эмфиземы. На сегодняшний день определен спектр генетических дефектов, в бóльшей или меньшей степени способных вызывать заболевание, определять его клинические проявления, тяжесть и частоту обострений.

Заключение

Заключение. Полноэкзомное секвенирование с определением пораженных метаболических путей дает возможность увидеть полный молекулярный «портрет» эмфиземы, определить эндотип и выбирать таргетную терапию для каждого отдельного клинического случая.

A personalized approach to the treatment of a polygenic disease, such as pulmonary emphysema, provides unique opportunities for selection of effective treatment in each clinical case. Progress of understanding molecular mechanisms behind emphysema allows to take a new look at classification, causes of phenotype variability, prognosis and preventive measures before clinical manifestation.

The aim of this review was to bring together the available data of genetic mutations impact to lung emphysema, its endotypes characteristics, and determine the personalized treatment approaches.

Results

Results. The attention of clinicians in the diagnosis of essential emphysema is focused on measurement the level of α1-antitrypsin in serum and mutations of SERPINA1 gene in exons 3, 4, 5 and 6. This is important, though not complete information about the causes and disease prognosis. This routine approach do not take into account the influence of genes-modifiers and gene-gene interactions. At the same time, intact SERPINA1 does not guarantee a zero risk of primary emphysema. To date, a wide range of genetic defects has been identified. These defects are capable, to a varying degree, to cause the disease, determine its clinical manifestations, severity and frequency of exacerbations.

Conclusion

Conclusion. Wholeexome sequencing with the identification of affected metabolic pathways makes it possible to see a complete molecular portrait of emphysema, determine the endotype and select targeted therapy for each clinical case.

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