vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-22-22vavilov-3294Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSРоль генов воспалительного ответа организма в формировании индивидуальных различий в уровне невербального интеллектаThe role of inflammatory system genes in individual differences in nonverbal intelligencehttps://orcid.org/0000-0002-4301-5283ЕникееваР. Ф.EnikeevaR. F.

Уфа

Ufa

Enikeevarf@gmail.comhttps://orcid.org/0000-0002-3744-8058КазанцеваА. В.KazantsevaA. V.

Уфа

Ufa

Kazantsa@mail.ruhttps://orcid.org/0000-0003-3508-4710ДавыдоваЮ. Д.DavydovaYu. D.

Уфа

Ufa

https://orcid.org/0000-0002-4091-382XМустафинР. Н.MustafinR. N.

Уфа

Ufa

ТахироваЗ. Р.TakhirovaZ. R.

Уфа

Ufa

https://orcid.org/0000-0002-3786-7447МалыхС. Б.MalykhS. B.

Москва

Moscow

https://orcid.org/0000-0001-9633-6374КовасЮ. В.KovasY. V.

Уфа

Лондон

Ufa

London

https://orcid.org/0000-0003-2987-3334ХуснутдиноваЭ. К.KhusnutdinovaE. K.

Уфа

Москва

Ufa

Moscow

Институт биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наук; Башкирский государственный университет, кафедра генетики и фундаментальной медицины, лаборатория нейрокогнитивной геномикиРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences; Bashkir State University, Department of genetics and fundamental medicine, Laboratory of neurocognitive genomicsRussian FederationБашкирский государственный университет, кафедра генетики и фундаментальной медицины, лаборатория нейрокогнитивной геномики; Башкирский государственный медицинский университет, кафедра медицинской генетики и фундаментальной медициныРоссияBashkir State University, Department of genetics and fundamental medicine, Laboratory of neurocognitive genomics; Bashkir State Medical University, Department of medical genetics and fundamental medicineRussian FederationБашкирский государственный университет, кафедра генетики и фундаментальной медицины, лаборатория нейрокогнитивной геномикиРоссияBashkir State University, Department of genetics and fundamental medicine, Laboratory of neurocognitive genomicsRussian FederationПсихологический институт Российской академии образования; Московский государственный университет им. M.В. Ломоносова, факультет психологииРоссияPsychological Institute of the Russian Academy of Education; Lomonosov Moscow State University, Department of psychologyRussian FederationБашкирский государственный университет, кафедра генетики и фундаментальной медицины, лаборатория нейрокогнитивной геномики; Голдсмит, Лондонский университет, международная лаборатория междисциплинарных исследований индивидуальных различий в обучении, департамент психологииРоссияBashkir State University, Department of genetics and fundamental medicine, Laboratory of neurocognitive genomics; Goldsmiths, University of London, Department of psychologyRussian FederationИнститут биохимии и генетики – обособленное структурное подразделение Уфимского федерального исследовательского центра Российской академии наук; Башкирский государственный университет, кафедра генетики и фундаментальной медицины, лаборатория нейрокогнитивной геномики; Московский государственный университет им. M.В. Ломоносова, факультет психологииРоссияInstitute of Biochemistry and Genetics – Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences; Bashkir State University, Department of genetics and fundamental medicine, Laboratory of neurocognitive genomics; Lomonosov Moscow State University, Department of psychologyRussian Federation202205042022262179187Copyright © Еникеева Р.Ф., Казанцева А.В., Давыдова Ю.Д., Мустафин Р.Н., Тахирова З.Р., Малых С.Б., Ковас Ю.В., Хуснутдинова Э.К., 20222022Еникеева Р.Ф., Казанцева А.В., Давыдова Ю.Д., Мустафин Р.Н., Тахирова З.Р., Малых С.Б., Ковас Ю.В., Хуснутдинова Э.К.Enikeeva R.F., Kazantseva A.V., Davydova Y.D., Mustafin R.N., Takhirova Z.R., Malykh S.B., Kovas Y.V., Khusnutdinova E.K.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3294

Невербальный интеллект – один из компонентов когнитивных функций мозга, использующий визуальные образы и невербальные методы для решения поставленных задач. Особую роль в развитии индивидуальных различий в уровне когнитивных функций мозга отводят взаимодействию нервной и иммунной систем. Гены, кодирующие про- и противовоспалительные цитокины, могут являться кандидатами при изуче- нии невербального интеллекта. Проведен анализ ассоциаций шести локусов генов, белковые продукты которых принимают участие в регуляции воспалительного ответа в центральной нервной системе: CRP (rs3093077), IL1А (rs1800587), IL1B (rs16944), TNF/LTA (rs1041981, rs1800629), P2RX7 (rs2230912), с уровнем невербального интеллекта у здоровых индивидов без когнитивных нарушений в возрасте 18–25 лет с включением половой, этнической принадлежности и наличия «рискового» аллеля ε4 гена APOE в качестве ковариат. С учетом важной роли средовых факторов, влияющих на формирование когнитивных функций мозга в целом и невербального интеллекта в частности, осуществлен анализ ген-средовых (G×E) взаимодействий. В результате статистического анализа показано, что полиморфные варианты rs1041981 и rs1800629 гена фактора некроза опухоли альфа (TNF) ассоциированы с фенотипическими вариациями в показателе невербального интеллекта на уровне гаплотипов (для гаплотипа АА: βST = 1.19; р = 0.033; pperm = 0.047) в группе носителей «рискового» варианта ε4 гена APOE. Построены модели ген-средовых взаимодействий, детерминирующие межиндивидуальные различия в уровне невербального интеллекта: число детей в семье и табакокурение модулируют ассоциацию вариантов генов TNF/LTA (rs1041981) (β = 2.08; βST = 0.16; p = 0.001) и P2RX7 (rs2230912) (β = –1.70; βST = –0.10; р = 0.022) c уровнем невербального интеллекта. Полученные данные свидетельствуют о том, что эффект гена TNF/LTA на формирование особенностей когнитивной сферы наблюдается только в случае наличия «неблагоприятного» варианта гена АРОЕ и при сочетании определенных социальных факторов.

Nonverbal intelligence represents one of the components of brain cognitive functions, which uses visual images and nonverbal approaches for solving required tasks. Interaction between the nervous and immune systems plays a specif ic role in individual differences in brain cognitive functions. Therefore, the genes encoding pro- and antiinf lammatory cytokines are prospective candidate genes in the study of nonverbal intelligence. Within the framework of the present study, we conducted the association analysis of six SNPs in the genes that encode proteins involved in inf lammatory response regulation in the central nervous system (CRP rs3093077, IL1А rs1800587, IL1B rs16944, TNF/ LTA rs1041981, rs1800629, and P2RX7 rs2230912), with nonverbal intelligence in mentally healthy young adults aged 18– 25 years without cognitive decline with inclusion of sex, ethnicity and the presence of the “risky” APOE ε4 allele as covariates. Considering an important role of environmental factors in the development of brain cognitive functions in general and nonverbal intelligence in particular, we conducted an analysis of gene-by-environment (G × E) interactions. As a result of a statistical analysis, rs1041981 and rs1800629 in the tumor necrosis factor gene (TNF) were shown to be associated with a phenotypic variance in nonverbal intelligence at the haplotype level (for АА-haplotype: βST = 1.19; p = 0.033; pperm = 0.047) in carriers of the “risky” APOE ε4 allele. Gene-by-environment interaction models, which determined interindividual differences in nonverbal intelligence, have been constructed: sibship size (number of children in a family) and smoking demonstrated a modulating effect on association of the TNF/LTA (rs1041981) (β = 2.08; βST = 0.16; p = 0.001) and P2RX7 (rs2230912) (β = –1.70; βST = –0.10; p = 0.022) gene polymorphisms with nonverbal intelligence. The data obtained indicate that the effect of TNF/LTA on the development of cognitive functions is evident only in the presence of the “unfavorable” APOE ε4 variant and/or certain environmental conditions.

невербальный интеллекткогнитивные функцииоднонуклеотидный полиморфный локусанализ ассоциациймикроглиявоспалительный ответnonverbal intelligencecognitive functionssingle nucleotide polymorphism (SNP)association analysismicrogliainf lammatory responseThe study was partially supported by the Russian Science Foundation (project No.17-78-30028) in the part of psychological assessment and collection of biological materials, by the Ministry of Science and Higher Education of Russian Federation (project No. 075-15-2021-595) in the part of statistical and bioinformatics analysis and by the mega-grant of the Ministry of Science and Higher Education of the Republic of Bashkortostan in the part of genetic analysis.ReferencesAlekseeva O.S., Kirik O.V., Gilerovich E.G., Korzhevskii D.E. Microglia of the brain: origin, structure and functions. Zhurnal Evolutsionnoy Biokhimii i Phiziologii = Journal of Evolutionary Biochemistry and Physiology. 2019;55(4):231-241. DOI 10.1134/S0044452919040028. 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The authors declare that there are no conflicts of interest present.