Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector122010.17816/ACEN.1220Original articlesОригинальные статьиResearch ArticlePolymorphisms in the SNCA gene and the risk of synucleopathyПолиморфные варианты гена SNCA и риск развития синуклеинопатийhttps://orcid.org/0000-0001-9419-1159AbramychevaNatalia Yu.АбрамычеваНаталья Юрьевна
Russian Federation

Cand. Sci. (Biol.), leading researcher, Head, Laboratory of molecular genetics, 5th Neurological department, Institute of Clinical and Preventive Neurology

канд. биол. наук, в. н. с., зав. молекулярно-генетической лабораторией 5-го неврологического отделения Института клинической и профилактической неврологии

abramicheva@neurology.ruhttps://orcid.org/0000-0002-5927-460XKaranLudmila S.КараньЛюдмила Станиславовна
Russian Federation

researcher, Laboratory of molecular genetics, 5th Neurological department, Institute of Clinical and Preventive Neurology

н. с. молекулярно-генетической лаборатории 5-го неврологического отделения Института клинической и профилактической неврологии

abramicheva@neurology.ruhttps://orcid.org/0000-0002-2798-0331ProtopopovaAnna O.ПротопоповаАнна Олеговна
Russian Federation

junior researcher, Laboratory of molecular genetics, 5th Neurological department, Institute of Clinical and Preventive Neurology

м. н. с. молекулярно-генетической лаборатории 5-го неврологического отделения Института клинической и профилактической неврологии

abramicheva@neurology.ruhttps://orcid.org/0000-0003-0728-8708MinaevIvan V.МинаевИван Вячеславович
Russian Federation

neurologist, 5th Neurological department, Institute of Clinical and Preventive Neurology

врач-невролог 5-го неврологического отделения Института клинической и профилактической неврологии

abramicheva@neurology.ruhttps://orcid.org/0009-0001-8707-180XBerdalinaIrina A.БердалинаИрина Александровна
Russian Federation

statistician, Department of highly qualified personnel training, Institute of Medical Education and Professional Development

статистик отдела подготовки кадров высшей квалификации Института медицинского образования и профессионального развития

abramicheva@neurology.ruhttps://orcid.org/0000-0001-8070-7644FedotovaEkaterina Yu.ФедотоваЕкатерина Юрьевна
Russian Federation

D. Sci. (Med.), leading researcher, Head, 5th Neurological department, Institute of Clinical and Preventive Neurology

д-р мед. наук, в. н. с., руководитель 5-го неврологического отделения Института клинической и профилактической неврологии

abramicheva@neurology.ruhttps://orcid.org/0000-0002-2704-6282IllarioshkinSergey N.ИллариошкинСергей Николаевич
Russian Federation

D. Sci. (Med.), Prof., RAS Full Member, Director, Brain Science Institute, Deputy Director for Science

д-р мед. наук, профессор, академик РАН, директор Института мозга, заместитель директора по научной работе

abramicheva@neurology.ruResearch Center of NeurologyНаучный центр неврологии1503202519143522510202425112024Copyright ©; 2025, Abramycheva N.Y., Karan L.S., Protopopova A.O., Minaev I.V., Berdalina I.A., Fedotova E.Y., Illarioshkin S.N.Copyright ©; 2025, Абрамычева Н.Ю., Карань Л.С., Протопопова А.О., Минаев И.В., Бердалина И.А., Федотова Е.Ю., Иллариошкин С.Н.2025Abramycheva N.Y., Karan L.S., Protopopova A.O., Minaev I.V., Berdalina I.A., Fedotova E.Y., Illarioshkin S.N.Абрамычева Н.Ю., Карань Л.С., Протопопова А.О., Минаев И.В., Бердалина И.А., Федотова Е.Ю., Иллариошкин С.Н.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/1220

Introduction. Synucleinopathies are mostly sporadic and multifactorial neurodegenerative disorders, which determines the involvement of various risk factors in their development. The polymorphic variants of the SNCA gene are considered as one of the predisposing genetic factors.

Study aim: to evaluate the effect of the 16 single nucleotide polymorphisms (SNP) located in various regulatory regions of the SNCA gene on the risk of developing three main forms of synucleinopathy — PD, DBL, and MSA — in Russian cohort of patients.

Materials and methods. The study included 73 PD patients, 46 MSA patients, 10 DLB patients, and 62 healthy volunteers. Genotyping of 16 SNPs of the SNCA gene was performed by direct Sanger sequencing on a capillary genetic analyzer. The Benjamini–Hochberg procedure was applied for multiple pairwise comparisons.

Results. A comparative case-control study showed that only one (rs11931074) of the 16 SNP analyzed was associated with PD: the minor T allele, located in the 3’-UTR region of the SNCA gene, increased the risk of PD (OR = 5.19; p < 0.05 (Benjamini–Hochberg adjusted p = 0.6)). An association with MSA was found for 11 of 16 SNP. The minor allele of 5 SNP (rs2619364, rs2619363, rs2619362, rs2619361, rs181489) reduced the risk of the disease, while for 6 SNP (rs7687945, rs2301134, rs2301135, rs3756063, rs2736990, rs11931074) increased the risk. The Benjamini–Hochberg procedure neutralized the significance of only one of these associations (rs181489).

Conclusion. This study is the first to genotype a large group of polymorphisms located in various regulatory regions of the SNCA gene and to establish significant associations with the risk of developing one of the forms of synucleinopathies, MSA, in the Russian population.

Введение. Большинство форм синуклеинопатий являются спорадическими и имеют многофакторную природу, что определяет участие различных факторов риска в их развитии. Как один из таких предрасполагающих генетических факторов рассматривается участие различных полиморфных вариантов гена SNCA.

Цель исследования: изучение влияния 16 однонуклеотидных полиморфных вариантов, локализованных в различных регуляторных областях гена SNCA, на риск развития в когорте пациентов российской популяции трёх основных форм синуклеинопатий: болезни Паркинсона (БП), деменции с тельцами Леви (ДТЛ) и мультисистемной атрофии (МСА).

Материалы и методы. В исследование были включены 73 пациента с БП, 46 с МСА, 10 с ДТЛ и 62 неврологически здоровых добровольца. Генотипирование 16 однонуклеотидных полиморфных вариантов (SNP) гена SNCA проводили методом прямого секвенирования по Сэнгеру на капиллярном генетическом анализаторе. Для коррекции ошибки при множественном попарном сравнении использовали поправку Беньямини–Хохберга.

Результаты. По результатам сравнительного анализа «диагноз–контроль» только 1 из 16 протестированных SNP (rs11931074), локализованный в области 3’-UTR гена SNCA, продемонстрировал связь с БП: минорный аллель T проявил тенденцию к увеличению риска развития БП (ОШ = 5,19; p < 0,05 (c поправкой Беньямини–Хохберга p = 0,6)). Для 11 из 16 SNP выявлена ассоциация с МСА. Минорный аллель 5 SNP из них (rs2619364, rs2619363, rs2619362, rs2619361, rs181489) снижал риск заболевания, а для 6 SNP (rs7687945, rs2301134, rs2301135, rs3756063, rs2736990, rs11931074) — повышал. Применение поправки Беньямини–Хохберга нивелировало значимость только одной из этих ассоциаций (rs181489).

Заключение. В результате проведённого исследования впервые генотипирована большая группа полиморфных вариантов, расположенных в различных регуляторных областях гена SNCA, и установлены значимые ассоциации с риском развития одной из форм синуклеинопатий — МСА — в российской популяции.

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