ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2022-4-105-113ssmu-5030Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSСредовые и генетические факторы риска болезни ПаркинсонаEnvironmental and genetic risk factors for Parkinson’s diseasehttps://orcid.org/0000-0002-2614-207XНикитинаМ. А.NikitinaM. A.

Никитина Мария Анатольевна – кандидат медицинских наук, доцент, кафедра неврологии и нейрохирургии

634050, г. Томск, Московский тракт, 2

2, Moscow Trakt, Tomsk, 634050

nikitina_ma@mail.ruhttps://orcid.org/0000-0002-4140-3223АлифироваВ. М.AlifirovaV. M.

Алифирова Валентина Михайловна – доктор медицинских наук, профессор, зав. кафедрой неврологии и нейрохирургии

634050, г. Томск, Московский тракт, 2

2, Moscow Trakt, Tomsk, 634050

v_alifirova@mail.ruhttps://orcid.org/0000-0002-1103-3073БрагинаЕ. Ю.BraginaE. Yu.

Брагина Елена Юрьевна – кандидат биологических наук, старший науч. сотрудник, лаборатория популяционной генетики

634050, г. Томск, ул. Набережная реки Ушайки, 10

10, Ushaika Embankment, Tomsk, 634050

elena.bragina@medgenetics.ruhttps://orcid.org/0000-0001-6133-8986БабушкинаН. П.BabushkinaN. P.

Бабушкина Надежда Петровна – кандидат биологических наук, науч. сотрудник, лаборатория популяционной генетики

634050, г. Томск, ул. Набережная реки Ушайки, 10

10, Ushaika Embankment, Tomsk, 634050

nad.babushkina@medgenetics.ruhttps://orcid.org/0000-0002-7882-2093ГомбоеваД. Е.GomboevaD. E.

Гомбоева Дѕнсѕма Евгеньевна – ординатор, лаборатория популяционной генетики

634050, г. Томск, ул. Набережная реки Ушайки, 10

10, Ushaika Embankment, Tomsk, 634050

Gombo-D@mail.ruhttps://orcid.org/0000-0002-0673-4094НазаренкоМ. С.NazarenkoS. M.

Назаренко Мария Сергеевна – доктор медицинских наук, профессор, вед. науч. сотрудник, лаборатория популяционной генетики, НИИ медицинской генетики, Томский НИМЦ; профессор кафедры медицинской генетики, СибГМУ

634050, г. Томск, ул. Набережная реки Ушайки, 10,

634050, г. Томск, Московский тракт, 2

2, Moscow Trakt, Tomsk, 634050,

10, Ushaika Embankment, Tomsk, 634050

maria.nazarenko@medgenetics.ruСибирский государственный медицинский университет (СибГМУ)РоссияSiberian State Medical UniversityRussian FederationНаучно-исследовательский институт (НИИ) медицинской генетики, Томский национальный исследовательский медицинский центр (НИМЦ) Российской академии наукРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center (NRMC), Russian Academy of SciencesRussian FederationСибирский государственный медицинский университет (СибГМУ); Научно-исследовательский институт (НИИ) медицинской генетики, Томский национальный исследовательский медицинский центр (НИМЦ) Российской академии наукРоссияSiberian State Medical University; Research Institute of Medical Genetics, Tomsk National Research Medical Center (NRMC), Russian Academy of SciencesRussian Federation202221012023214105113Copyright © Никитина М.А., Алифирова В.М., Брагина Е.Ю., Бабушкина Н.П., Гомбоева Д.Е., Назаренко М.С., 20232023Никитина М.А., Алифирова В.М., Брагина Е.Ю., Бабушкина Н.П., Гомбоева Д.Е., Назаренко М.С.Nikitina M.A., Alifirova V.M., Bragina E.Y., Babushkina N.P., Gomboeva D.E., Nazarenko S.M.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/5030Цель

Цель. Проанализировать факторы риска в группе пациентов с болезнью Паркинсона (БП) и сопоставить их с литературными данными.

Материалы и методы

Материалы и методы. В исследование были включены 439 пациентов с БП и 354 индивида группы контроля, сопоставимых по полу и возрасту. На каждого индивидуума заполнена регистрационная карта, содержащая информацию о демографических, эпидемиологических, клинических и нейропсихологических данных. Тяжесть заболевания исследовалась по шкале MDS-UPDRS; стадия БП – согласно шкале Hoehn – Yahr. Когнитивные функции оценивались по MoCA-тесту и MMSE. Длину (CAG)n-повтора в гене HTT определяли с помощью фрагментного анализа на платформе ABI Genetic Analyzer 3730. Анализ полученных результатов проводился с помощью GeneMapper Software v4.1 (Applied Biosystems, США).

Результаты

Результаты. При сравнении пациентов с БП и контрольной выборки отношение шансов развития БП у индивидов с травмой головы составило 3,13 (95% CI: 2,27–4,34; p = 4,94 × 10–13), показав значимость этого фактора риска БП. Употребление в анамнезе кофе отличает группу пациентов с БП от группы контроля (OR = 0,41 (95% CI: 0,30–0,56); p < 0,0001), подтверждая его нейропротективное действие. Анализ вариабельности длины (CAG)n-повторов в гене HTT показал, что пациенты, в генотипе которых присутствует аллель, содержащий 17 повторов в сочетании с любым другим аллелем, кроме аллеля, содержащего 18 повторов, обладает протективным эффектом (OR = 0,50 (95% CI: 0,27–0,92); p = 0,025). Все генотипы, содержащие аллель с 18 повторами, предрасполагают к БП (OR = 2,57 (95% CI: 1,66–4,28); p = 0,007). Предрасполагающий эффект аллеля, не связанный с экспансией CAG-повторов гена HTT, к БП выявлен впервые.

Заключение

Заключение. Черепно-мозговая травма и аллель (CAG)18-повторов гена HTT являются факторами риска для развития БП. Употребление кофе можно отнести к протективным факторам в отношении БП.

Aim

Aim. To analyze risk factors in the group of patients with Parkinson’s disease (PD) and compare them with the literature data.

Materials and methods

Materials and methods. The study included 439 patients with PD and 354 controls, comparable by gender and age. For each individual, a registration card was filled in containing demographic, epidemiological, clinical, and neuropsychological data. The severity of the disease was studied according to the MDS-UPDRS scale; the stage of PD was determined according to the Hoehn and Yahr scale. Cognitive functions were assessed by the MoCA test and MMSE. The length of the (CAG)n repeat region in the HTT gene was determined using fragment analysis on the ABI 3730 DNA analyzer. The obtained results were analyzed using GeneMapper Software v4.1 (Applied Biosystems, USA).

Results

Results. When comparing patients with PD and the control group, the odds ratio (OR) for PD in individuals with traumatic brain injury was 3.13 (95% confidence interval (CI): 2,27–4.34; p = 4.94 × 10–13), which showed the significance of this risk factor for PD. Consumption of coffee in the anamnesis distinguished the group of PD patients from the control group (OR = 0.41 (95% CI: 0.30–0.56); p < 0.0001), confirming its neuroprotective effect. Analysis of the variability in the length of the (CAG)n repeat regions in the HTT gene showed that patients whose genotype contained an allele with 17 repeats in combination with any allele other than an allele containing 18 repeats had a protective effect (OR = 0.50 (95% CI: 0.27–0.92); p = 0.025). All genotypes containing an allele with 18 repeats were predisposed to PD (OR = 2.57 (95% CI: 1.66–4.28); p = 0.007). The predisposing effect of the allele to PD, unrelated to the expansion of CAG repeats in the HTT gene, was revealed for the first time.

Conclusion

Conclusion. Traumatic brain injury and the allele with 18 CAG repeats in the HTT gene are risk factors for PD. Coffee consumption can be attributed to protective factors in relation to PD.

болезнь Паркинсонафакторы рискакофечерепно-мозговая травмаHTTParkinson’s diseaserisk factorscoffeetraumatic brain injuryHTT geneИсследование выполнено при частичной грантовой поддержке научно-исследовательских проектов, выполняемых молодыми учеными («Роль генов репарации в патогенезе болезни Паркинсона, болезни Гентингтона и нормального (здорового) старения», 2021–2023 гг.). Работа выполнена при частичном финансировании Министерства науки и высшего образования (госзадание № 122020300041-7)The study was partially supported by the research grants for young scientists (“The role of repair genes in the pathogenesis of Parkinson's disease, Huntington's disease, and healthy ageing” 2021–2023). The study was partially supported by the state assignment of the Ministry of Science and Higher Education No.122020300041-7ReferencesObeso J.A., Stamelou M., Goetz C.G., Poewe W., Lang A.E., Weintraub D. et al. 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The authors declare that there are no conflicts of interest present.