Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66720310.31857/S0016675824090094adlqwzГЕНЕТИКА ЧЕЛОВЕКАResearch ArticleAssociation of long non-coding RNA genes (H19, MEG3, MALAT1, Linc00305, Linc00261, Linc02227, and CDKN2B-AS1) polymorphic loci with chronic obstructive pulmonary diseaseАссоциация полиморфных локусов генов длинных некодирующих РНК (H19, MEG3, MALAT1, Linc00305, Linc00261, Linc02227 и CDKN2B-AS1) с хронической обструктивной болезнью легкихKorytinaG. F.КорытинаГ. Ф.
Russian Federation
guly_kory@mail.ruAkhmadishinaL. Z.АхмадишинаЛ. З.
Russian Federation
guly_kory@mail.ruMarkelovV. A.МаркеловВ. А.
Russian Federation
guly_kory@mail.ruNasibullinT. R.НасибуллинТ. Р.
Russian Federation
guly_kory@mail.ruAznabaevaY. G.АзнабаеваЮ. Г.
Russian Federation
guly_kory@mail.ruKochetovaO. V.КочетоваО. В.
Russian Federation
guly_kory@mail.ruKhusnutdinovaN. N.ХуснутдиноваН. Н.
Russian Federation
guly_kory@mail.ruLarkinaA. P.ЛаркинаА. П.
Russian Federation
guly_kory@mail.ruZagidullinN. S.ЗагидуллинН. Ш.
Russian Federation
guly_kory@mail.ruVictorovaT. V.ВиктороваТ. В.
Russian Federation
guly_kory@mail.ruInstitute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of SciencesИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукBashkir State Medical UniversityБашкирский государственный медицинский университетUfa State Petroleum Technological UniversityУфимский государственный нефтяной технический университет10092024609748926022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/667203

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease resulting from dynamic, cumulative gene-environment interactions that cause lung tissue injury, alteration of its normal function and acceleration of cellular senescence. Long non-coding RNAs (lncRNAs) function as critical epigenetic regulators of various aspects of cellular senescence. The objective of the present study is to identify the association between polymorphic variants of H19 (rs3741219), MEG3 (rs7158663), MALAT1 (rs619586), LINC00305 (rs2850711), LINC00261 (rs6048205), CDKN2B-AS1 (rs4977574), and LINC02227 (rs2149954) lncRNAs genes with COPD. DNA samples from COPD patients (N = 703) and healthy individuals (N = 655) were studied in this study and polymorphic loci were analyzed by real–time PCR. Association with COPD was established with H19 (rs3741219), MEG3 (rs7158663), LINC02227 (rs2149954), MALAT1 (rs619586) and CDKN2B-AS1 (rs4977574). Polygenic analysis has allowed to identify informative gene-gene combinations that include polymorphic variants of the studied lncRNAs genes and genes encoding molecules of signaling cascades associated with cellular senescence and apoptosis. Multiple regression and ROC-analysis revealed a COPD risk predictive model, which included gene–gene combinations of lncRNAs genes and smoking index (P = 4.01 x 10-48, AUC = 0.87).

Хроническая обструктивная болезнь легких (ХОБЛ) – это хроническое заболевание, возникающее в результате динамических, кумулятивных ген–средовых взаимодействий, результатом которых является повреждение легочной ткани и изменение ее нормального функционирования, связанное с ускоренным клеточным старением. Длинные некодирующие РНК (днРНК) являются важными эпигенетическими регуляторами различных аспектов клеточного старения. Цель настоящего исследования – выявление ассоциации полиморфных вариантов генов днРНК H19, MEG3, MALAT1, Linc00305, Linc00261, CDKN2B-AS, Linc02227 с ХОБЛ. В работе были использованы образцы ДНК больных ХОБЛ (N = 703) и здоровых индивидов (N = 655), полиморфные локусы анализировали методом ПЦР в реальном времени. Ассоциация с развитием ХОБЛ была установлена для генов H19 (rs3741219), MEG3 (rs7158663), Linc02227 (rs2149954), MALAT1 (rs619586) и CDKN2B-AS1 (rs4977574). Полигенный анализ позволил выявить информативные ген–генные комбинации, включающие полиморфные варианты днРНК и генов, кодирующих компоненты молекулярных каскадов, связанных с клеточным старением и апоптозом. По результатам множественного регрессионного и ROC-анализа получена прогностическая модель формирования ХОБЛ, в которую вошли ген–генные комбинации и индекс курения (P = 4.01 x 10–48, AUC = 0.87).

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