References

vavilov

Вавиловский журнал генетики и селекции

Vavilov Journal of Genetics and Breeding

2500-3259

Institute of Cytology and Genetics of Siberian Branch of the RAS

10.18699/VJ19.531

vavilov-2212

Research Article

БИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУ

MEDICAL GENETICS

Эпигенетика суицидального поведения

Epigenetics of suicidal behavior

https://orcid.org/0000-0002-4091-382X

Мустафин

Р. Н.

Mustafin

R. N.

ruji79@mail.ru

https://orcid.org/0000-0002-3744-8058

Казанцева

А. В.

Kazantseva

A. V.

https://orcid.org/0000-0002-4301-5283

Еникеева

Р. Ф.

Enikeeva

R. F.

https://orcid.org/0000-0003-3508-4710

Давыдова

Ю. Д.

Davydova

Yu. D.

https://orcid.org/0000-0002-3786-7447

Малых

С. Б.

Malykh

S. B.

Викторов

В. В.

Viktorov

V. V.

https://orcid.org/0000-0003-2987-3334

Хуснутдинова

Э. К.

Khusnutdinova

E. K.

Башкирский государственный медицинский университет; Башкирский государственный университетРоссияBashkir State Medical University; Bashkir State UniversityRussian Federation

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 Federation

Башкирский государственный университет; Институт биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияBashkir State University; Institute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre, RASRussian Federation

Психологический институт Российской академии образованияРоссияPsychological Institute of the Russian Academy of EducationRussian Federation

Башкирский государственный медицинский университетРоссияBashkir State Medical UniversityRussian Federation

Башкирский государственный медицинский университет; Башкирский государственный университет; Институт биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наукРоссияBashkir State Medical University; Bashkir State University; Institute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre, RASRussian Federation

2019

23082019

235600607

2019

Мустафин Р.Н., Казанцева А.В., Еникеева Р.Ф., Давыдова Ю.Д., Малых С.Б., Викторов В.В., Хуснутдинова Э.К.

Mustafin R.N., Kazantseva A.V., Enikeeva R.F., Davydova Y.D., Malykh S.B., Viktorov V.V., Khusnutdinova E.K.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://vavilov.elpub.ru/jour/article/view/2212

Самоубийства занимают второе место среди причин смерти среди молодежи, в связи с чем являются серьезной глобальной проблемой человечества. Для разработки перспективных методов диагностики и лечения данной патологии важное значение имеет исследование генетических и эпигенетических факторов в развитии суицидального поведения. Роль наследственных факторов в развитии суицидального поведения оценивается в 30–55 %, при этом характерна выраженная коморбидность с другими психическими расстройствами. Для исследования генетической предрасположенности к суициду используются молекулярно-генетические методы, включая контролируемые анализы ассоциаций и сцепления, микроматричные анализы экспрессии генов и полногеномный поиск ассоциаций. В литературе представлены данные об идентификации множества генов, в том числе связанных с изменениями функционирования серотонинергической (гены SLC6A4, TPH, 5-HT1A), гипоталамо-гипофизарно-надпочечниковой систем (ген FKBP5) и полиаминов (гены SAT и OATL1), ассоциированных с развитием суицидального поведения. Однако разнообразие взаимодействующих генетических локусов усложняет интерпретацию развития сложного фенотипа патологии и не позволяет определить выраженную ассоциацию. Для разрешения данной проблемы и интерпретации недостающей связи между окружающей средой и геномом были получены многообещающие результаты при изучении эпигенетических факторов, роль которых при суицидальном поведении показана в изменении экспрессии головного мозга. Уникальным объектом для прямого исследования изменения геномных процессов является головной мозг умерших от суицида людей, при изучении которого был выявлен широкий спектр репрограммирования паттернов ДНК-метилирования промоторов генов системы полиаминов (OAZ1, OAZ2, AMD1, ARG2, SKA2), серотонинергической (SLC6A4) и ГАМК-ергической (GABRA1) систем, глюкокортикоидных (GR, NR3C1) и тирозинкиназных (TrkB) рецепторов, нейротрофического фактора головного мозга (BDNF). Показана роль изменений модификации гистонов в области расположения специфических генов (Cx30, Cx43, TrkB.T1) и экспрессии специфических длинных некодирующих РНК и микроРНК в развитии суицидального поведения, что перспективно для разработки программ диагностических алгоритмов и таргетной терапии.

Suicide is the second leading cause of death among young people and therefore being a serious global problem worldwide. The study of genetic and epigenetic factors in the development of suicidal behavior plays an important role in the development of advanced methods of diagnosis and treatment of this pathology. The role of hereditary factors in the development of suicidal behavior is estimated at 30–55 %, with a pronounced comorbidity with other psychopathologies. The study of genetic liability to suicidal behavior is based on molecular-genetic methods including association and linkage analyses, chip gene expression arrays, and genome-wide association studies. Published data identified multiple genes including those involved in the functioning of serotonergic (SLC6A4, TPH, 5-HT1A), hypothalamic-pituitary-adrenal systems (FKBP5) and polyamines (SAT and OATL1) associated with suicidal behavior. However, the diversity of interacting genetic loci complicates the interpretation of the development of a complex phenotype of pathology and prevents the association from being detected. To solve this problem and interpret the missing relationship between the environment and the genome, promising results were obtained from a study of epigenetic factors, which affected the expression of a number of candidate genes involved in brain functioning in suicidal behavior. The analysis of a brain obtained from suicide victims, representing a unique tool for the analysis of modified genomic processes, revealed a wide range of reprogramming patterns of DNA methylation in promoters of the genes of polyamine (OAZ1, OAZ2, AMD1, ARG2, SKA2), serotonergic (SLC6A4) and GABAergic (GABRA1) systems, HPA-axis (GR, NR3C1), tyrosine kinase (TrkB) receptors, brain-derived neurotrophic factor (BDNF). The role of histone modifications in distinct genes (Cx30, Cx43, TrkB.T1) and the expression of specific long noncoding RNAs and microRNAs in the development of suicidal behavior, which is promising for the development of diagnostic algorithms and target therapy, is discussed.

ассоциацииголовной мозгметилированиенекодирующие РНКсуицидэпигенетика

associationbrainmethylationnon-coding RNAssuicideepigenetics

This review was supported by the Russian Science Foundation, project 19-78-30021 “Risks of suicidal behavior development: genetic and epigenetic mechanisms”, and the Russian Foundation for Basic Research, project 17-29-02195 “Genomics of aggressive and depressive human behavior”.

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