actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2022-7.6.2actabiomedica-3878Research ArticleДИСКУССИОННЫЕ СТАТЬИ, ЛЕКЦИИ, НОВЫЕ ТРЕНДЫ МЕДИЦИНСКОЙ НАУКИDISCUSSION PAPERS, LECTURES, NEW TRENDS IN MEDICAL SCIENCEАссоциации генов систем репарации ДНК с болезнью ПаркинсонаAssociations of genes of DNA repair systems with Parkinson’s diseasehttps://orcid.org/0000-0001-6133-8986БабушкинаН. П.BabushkinaN. P.

 Бабушкина Надежда Петровна – кандидат биологических наук, научный сотрудник лаборатории популяционной генетики

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

Nadezhda P.  Babushkina  – Cand. Sc. (Biol.), Research Officer at the Laboratory of Population Genetics

 Ushaika embankment 10, Tomsk 634050, Russian Federation 

nad.babushkina@medgenetics.ruhttps://orcid.org/0000-0002-2614-207XНикитинаМ. А.NikitinaM. A.

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

634050, г. Томск, Московский тракт, 2, Россия

Maria A. Nikitina– Cand. Sc. (Med.), Associate Professor at the Department of Neurology and Neurosurgery 

Moskovsky tract 2, Tomsk 634050, Russian Federation 

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

Брагина Елена Юрьевна – кандидат биологических наук, старший научный сотрудник лаборатории популяционной генетики

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

Elena Yu. Bragina – Cand. Sc. (Biol.), Senior Research Officer at the Laboratory of Population Genetics 

 Ushaika embankment 10, Tomsk 634050, Russian Federation 

elena.bragina@medgenetics.ruhttps://orcid.org/0000-0002-4140-3223АлифироваВ. М.AlifirovaV. M.

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

634050, г. Томск, Московский тракт, 2, Россия

Valentina M. Alifirova– Dr. Sc. (Med.), Professor, Head of the Department of Neurology and Neurosurgery 

Moskovsky tract 2, Tomsk 634050, Russian Federation 

v_alifirova@mail.ruhttps://orcid.org/0000-0002-5144-001XПостриганьА. Е.PostriganA. E.

Постригань Анна Евгеньевна – младший научный сотрудник лаборатории геномики орфанных болезней 

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

Anna E. Postrigan – Junior Research Officer at the Laboratory of Orphan Diseases Genomics 

 Ushaika embankment 10, Tomsk 634050, Russian Federation 

postrigan.anna@medgenetics.ruhttps://orcid.org/0000-0003-1905-3324ДевяткинаЕ. А.DeviatkinaYe. A.

Девяткина Екатерина Алексеевна – студентка

634050, г. Томск, Московский тракт, 2, Россия

Yekaterina A. Deviatkina – Student 

Moskovsky tract 2, Tomsk 634050, Russian Federation 

271297rfnz@list.ruhttps://orcid.org/0000-0002-7882-2093ГомбоеваД. Е.GomboevaD. E.

Гомбоева Дэнсэма Евгеньевна – ординатор

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

Densema E. Gomboeva – Clinical Resident 

 Ushaika embankment 10, Tomsk 634050, Russian Federation 

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

Назаренко Мария Сергеевна – доктор медицинских наук, ведущий научный сотрудник лаборатории популяционной генетики; профессор кафедры медицинской генетики 

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

634050, г. Томск, Московский тракт, 2, Россия

Maria S. Nazarenko – Dr. Sc. (Med.), Leading Research Officer at the Laboratory of Population Genetics; Professor at the Department of Medical Genetics 

Ushaika embankment 10, Tomsk 634050, Russian Federation 

Moskovsky tract 2, Tomsk 634050, Russian Federation 

maria.nazarenko@medgenetics.ruНаучно-исследовательский институт медицинской генетики, ФГБНУ «Томский национальный исследовательский медицинский центр РАН»Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииSiberian State Medical UniversityНаучно-исследовательский институт медицинской генетики, ФГБНУ «Томский национальный исследовательский медицинский центр РАН»Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of SciencesНаучно-исследовательский институт медицинской генетики, ФГБНУ «Томский национальный исследовательский медицинский центр РАН»; ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииResearch Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical University202229122022761221Copyright © Бабушкина Н.П., Никитина М.А., Брагина Е.Ю., Алифирова В.М., Постригань А.Е., Девяткина Е.А., Гомбоева Д.Е., Назаренко М.С., 20222022Бабушкина Н.П., Никитина М.А., Брагина Е.Ю., Алифирова В.М., Постригань А.Е., Девяткина Е.А., Гомбоева Д.Е., Назаренко М.С.Babushkina N.P., Nikitina M.A., Bragina E.Y., Alifirova V.M., Postrigan A.E., Deviatkina Y.A., Gomboeva D.E., Nazarenko M.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/3878

Актуальность. Примерно 5–10 % случаев болезни Паркинсона (БП) являются моногенными, в остальных случаях патология имеет многофакторную природу. Одним из признанных патогенетических путей БП является митохондриальная дисфункция, в частности накопление повреждений в митохондриальной ДНК. Соответственно, гены белков систем репарации ДНК являются перспективными генами-кандидатами для многофакторных форм БП.Цель исследования. Пилотное изучение вовлечённости генов белков систем репарации ДНК в развитие болезни Паркинсона.Материалы и методы. Ассоциативный анализ проведён при сравнении группы пациентов с БП (n = 133) с популяционной выборкой г. Томска (n = 344). Методом SNaPshot-анализа изучены 8 SNP в генах белков систем репарации ДНК (rs560191 (TP53BP1); rs1805800 и rs709816 (NBN); rs473297 (MRE11A); rs1189037 и rs1801516 (ATM); rs1799977 (MLH1); rs1805321 (PMS2)).Результаты. К развитию БП предрасполагают частые аллели и гомозиготные по ним генотипы rs1801516 в гене ATM (отношение шансов (OR, odds ratio) – 3,27 (p = 0,000004) и OR = 3,46 (p = 0,00008) для рисковых аллеля и генотипа соответственно) и rs1799977 в гене MLH1 (OR = 1,88 (p = 0,0004) и OR = 2,42 (p = 0,00007) соответственно); гетерозиготы обладают протективным эффектом (OR = 0,33 (p = 0,0007) и OR = 0,46 (p = 0,0007) для ATM и MLH1 соответственно). Также к БП предрасполагают редкий аллель rs1805800 в гене NBN (OR = 1,62 (p = 0,019)) и гомозиготный по нему генотип (OR = 2,28 (p = 0,016)). Ассоциации с БП генов ATM, MLH1, NBN выявлены впервые. Заключение. Нарушение функционирования митохондрий является одним из ключевых в патогенезе БП; при этом по меньшей мере два из трёх белковых продукта ассоциированных генов вовлечены в развитие дисфункции митохондрий. Соответственно, можно предположить вовлеченность ассоциированных генов в патогенез БП именно через митохондриальную дисфункцию.

Background. Approximately 5–10 % of cases of Parkinson’s disease (PD) are monogenic, in other cases the pathology has a multifactorial etiology. One of recognized pathogenetic pathways of PD is mitochondrial dysfunction, in particular the accumulation of damage in mitochondrial DNA. Hence, the genes of DNA repair proteins are promising candidate genes for multifactorial forms of PD.The aim. To study the involvement of genes of DNA repair proteins in the development of Parkinson’s disease.Materials and methods. The associative analysis was carried out while comparing a group of patients with PD (n = 133) with a Tomsk population sample (n = 344). SNaPshot analysis was used to study 8 SNPs in genes of DNA repair proteins (rs560191 (TP53BP1); rs1805800 and rs709816 (NBN); rs473297 (MRE11A); rs1189037 and rs1801516 (ATM); rs1799977 (MLH1); rs1805321 (PMS2)).Results. Common alleles and homozygous rs1801516 genotypes in the ATM gene predispose the development of PD (odds ratio (OR) – 3.27 (p = 0.000004) and OR = 3.46 (p = 0.00008) for risk alleles and genotype respectively) and rs1799977 in the MLH1 gene (OR = 1.88 (p = 0.0004) and OR = 2.42 (p = 0.00007) respectively); heterozygotes have a protective effect (OR = 0.33 (p = 0.0007) and OR = 0.46 (p = 0.0007) for ATM and MLH1, respectively). The rare rs1805800 allele in the NBN gene (OR = 1.62 (p = 0.019)) and a homozygous genotype for it (OR = 2.28 (p = 0.016)) also predispose to PD. Associations with PD of the ATM, MLH1, NBN genes were revealed for the first time.Conclusion. Mitochondrial dysfunction is one of the key factors in the pathogenesis of PD, while at least two of the three protein products of associated genes are involved in the development of mitochondrial dysfunction. Accordingly, it can be assumed that associated genes are involved in the pathogenesis of PD precisely through mitochondrial dysfunction.

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