vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ19.515vavilov-2140Research ArticleГЕНЕТИКА ЧЕЛОВЕКАHUMAN GENETICSГенетические основы предрасположенности к депрессивным расстройствамGenetic basis of depressive disordershttps://orcid.org/0000-0003-3508-4710ДавыдоваЮ. Д.DavydovaYu. D.julia.dmitrievna@list.ruhttps://orcid.org/0000-0002-4301-5283ЕникееваР. Ф.EnikeevaR. F.https://orcid.org/0000-0002-3744-8058КазанцеваА. В.KazantsevaA. V.https://orcid.org/0000-0002-4091-382XМустафинР. Н.MustafinR. N.РомановаА. Р.RomanovaA. R.https://orcid.org/0000-0002-3786-7447МалыхС. Б.MalykhS. B.https://orcid.org/0000-0003-2987-3334ХуснутдиноваЭ. К.KhusnutdinovE. K.Институт биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre, RASRussian FederationБашкирский государственный университет; Башкирский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияBashkir State University; Bashkir State Medical University of the Ministry of Health of the Russian FederationRussian FederationСтерлитамакский филиал Башкирского государственного университетаРоссияSterlitamak Branch of the Bashkir State UniversityRussian FederationПсихологический институт Российской академии образованияРоссияPsychological Institute of Russian Academy of EducationRussian FederationИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наук; Башкирский государственный университетРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre, RAS; Bashkir State UniversityRussian Federation201907072019234465472Copyright © Давыдова Ю.Д., Еникеева Р.Ф., Казанцева А.В., Мустафин Р.Н., Романова А.Р., Малых С.Б., Хуснутдинова Э.К., 20192019Давыдова Ю.Д., Еникеева Р.Ф., Казанцева А.В., Мустафин Р.Н., Романова А.Р., Малых С.Б., Хуснутдинова Э.К.Davydova Y.D., Enikeeva R.F., Kazantseva A.V., Mustafin R.N., Romanova A.R., Malykh S.B., Khusnutdinov E.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/2140

Депрессия – это распространенное психическое расстройство, которое является одной из ведущих причин нетрудоспособности и смертности в мире. Несмотря на интенсивные исследования, проводимые в течение последних десятилетий, этиология депрессивных расстройств все еще остается не до конца изученной, однако генетические факторы, безусловно, играют важную роль в предрасположенности к депрессии. Настоящий обзор сфокусирован на результатах работ, основанных на генно-кандидатном подходе, полногеномных (Genome-Wide Association Studies, GWAS) и полноэкзомных (Whole Exome Sequencing, WES) исследованиях, продемонстрировавших связь полиморфных локусов генов с депрессивными расстройствами. Согласно первому подходу, формирование депрессивной симптоматики находится под влиянием генов серотонинергической (TPH1, TPH2, HTR1A, HTR2A, SLC6A4), дофаминергической (DRD4, SLC6A3) и норадренергической (SLC6A2) систем, а также генов ферментов их метаболизма (MAOA, COMT). Кроме того, имеются данные об участии генов гипоталамо-гипофизарной системы (OXTR, AVPR1A, AVPR1B) и рецепторов половых гормонов (ESR1, ESR2, AR), генов нейротрофического фактора мозга (BDNF) и фермента метилентетрагидрофолатредуктазы (MTHFR), нейронального апоптоза (CASP3, BCL-XL, BAX, NPY, APP, GRIN1) и воспалительной системы (TNF, CRP, IL6, IL1B, PSMB4, PSMD9, STAT3) в развитии депрессивных расстройств. Результаты второго подхода  (GWAS и WES) демонстрируют, что гены белков пикколо (PCLO) и сиртуина (SIRT1), фактора пролиферации стволовых клеток (GNL3), гликозилтрансферазы (GLT8D1), α-трипсинового ингибитора (ITIH3), мелатонинового рецептора (MTNR1A), костного морфогенного белка (BMP5), ломкой гистидиновой триады (FHIT) и киназного супрессора (KSR2), протокадгерина (PCDH9) и активатора транскрипции AUTS2, преимущественно участвующие в процессах нейрогенеза и клеточной адгезии, вовлечены в развитие депрессии. Таким образом, эти и другие литературные данные подтверждают, что формирование генетической предрасположенности к депрессивным расстройствам – сложный процесс, затрагивающий функционирование большого числа генов, в том числе тех, которые ранее не обсуждались в связи с депрессией, что требует обратить особое внимание на них в дальнейших исследованиях.

Depression is a common mental disorder being one of the main causes of disability and mortality worldwide. Despite an intensive research during the past decades, the etiology of depressive disorders (DDs) remains incompletely understood; however, genetic factors are significantly involved in the liability to depression. The present review is focused on the studies based on a candidate gene approach, genome-wide association studies (GWAS) and whole exome sequencing (WES), which previously demonstrated associations between gene polymorphisms and DDs. According to the first approach, DD development is affected by serotonergic (TPH1, TPH2, HTR1A, HTR2A, and SLC6A4), dopaminergic (DRD4, SLC6A3) and noradrenergic (SLC6A2) system genes, and genes of enzymatic degradation (MAOA, COMT). In addition, there is evidence of the involvement of HPA-axis genes (OXTR, AVPR1A, and AVPR1B), sex hormone receptors genes (ESR1, ESR2, and AR), neurotrophin (BDNF) and methylenetetrahydrofolate reductase (MTHFR) genes, neuronal apoptosis (CASP3, BCL-XL, BAX, NPY, APP, and GRIN1) and inflammatory system (TNF, CRP, IL6, IL1B, PSMB4, PSMD9, and STAT3) genes in DD development. The results of the second approach (GWAS and WES) revealed that the PCLO, SIRT1, GNL3, GLT8D1, ITIH3, MTNR1A, BMP5, FHIT, KSR2, PCDH9, and AUTS2 genes predominantly responsible for neurogenesis and cell adhesion are involved in liability to depression. Therefore, the findings discussed suggest that genetic liability to DD is a complex process, which assumes simultaneous functioning of multiple genes including those reported previously, and requires future research in this field.

 

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