<?xml version='1.0' encoding='utf-8'?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd">
<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2022-8-2-0-2</article-id><article-id pub-id-type="publisher-id">2717</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;The association of inflammatory status and immunological parameters with single-nucleotide polymorphisms of cytokine and Toll-like receptor genes in patients with schizophrenia&lt;/strong&gt;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;The association of inflammatory status and immunological parameters with single-nucleotide polymorphisms of cytokine and Toll-like receptor genes in patients with schizophrenia&lt;/strong&gt;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Malashenkova</surname><given-names>Irina K.</given-names></name><name xml:lang="en"><surname>Malashenkova</surname><given-names>Irina K.</given-names></name></name-alternatives><email>malashenkova.irina@bk.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Ushakov</surname><given-names>Vadim L.</given-names></name><name xml:lang="en"><surname>Ushakov</surname><given-names>Vadim L.</given-names></name></name-alternatives><email>tiuq@yandex.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Krynskiy</surname><given-names>Sergey A.</given-names></name><name xml:lang="en"><surname>Krynskiy</surname><given-names>Sergey A.</given-names></name></name-alternatives><email>srgkr002@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Ogurtsov</surname><given-names>Daniil P.</given-names></name><name xml:lang="en"><surname>Ogurtsov</surname><given-names>Daniil P.</given-names></name></name-alternatives><email>ogurtsovdp@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Khailov</surname><given-names>Nikita A.</given-names></name><name xml:lang="en"><surname>Khailov</surname><given-names>Nikita A.</given-names></name></name-alternatives><email>nik_khailov@bk.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Moskvina</surname><given-names>Svetlana N.</given-names></name><name xml:lang="en"><surname>Moskvina</surname><given-names>Svetlana N.</given-names></name></name-alternatives><email>kasya45@yandex.ru</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Zakharova</surname><given-names>Natalia V.</given-names></name><name xml:lang="en"><surname>Zakharova</surname><given-names>Natalia V.</given-names></name></name-alternatives><email>nataliza80@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Chekulaeva</surname><given-names>Ekaterina I.</given-names></name><name xml:lang="en"><surname>Chekulaeva</surname><given-names>Ekaterina I.</given-names></name></name-alternatives><email>chekulaevakatarina@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Didkovsky</surname><given-names>Nikolay A.</given-names></name><name xml:lang="en"><surname>Didkovsky</surname><given-names>Nikolay A.</given-names></name></name-alternatives><email>didkovskinic@gmail.com</email></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Kostyuk</surname><given-names>Georgy P.</given-names></name><name xml:lang="en"><surname>Kostyuk</surname><given-names>Georgy P.</given-names></name></name-alternatives><email>kgr@yandex.ru</email></contrib></contrib-group><pub-date pub-type="epub"><year>2022</year></pub-date><volume>8</volume><issue>2</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2022/2/Биомедицинские_исследования_июнь_2022-16-31.pdf" /><abstract xml:lang="ru"><p>Background:&amp;nbsp;Schizophrenia is a multifactorial and clinically polymorphic disease with a significant hereditary component. The study of the influence of functionally significant polymorphisms of the genes regulating immune response and inflammation on the immune parameters in patients with schizophrenia is relevant for the development of new methods for predicting the course of the disease and finding new therapy targets. The aim of the study:&amp;nbsp;To study the association of polymorphisms in cytokine and Toll-like receptor genes with the serum levels of immune mediators in patients with schizophrenia. Materials and methods:&amp;nbsp;95 patients diagnosed with schizophrenia and 99 healthy volunteers were recruited into the study. Polymorphisms of genes regulating the immune response (IL1B rs1143627, IL4 rs2243250, IL2 rs2069762, IL10 (rs1800896, rs1800872, rs1800871), IFNL rs8099917, IFNL rs12979860, TLR9 rs5743836, TLR9 rs352140, TLR3 rs3775291), the serum level of major cytokines and markers of systemic inflammation were determined. Results:&amp;nbsp;The patients were found to have elevated levels of key pro-inflammatory cytokines IL-8 and IL-17A and other markers of systemic inflammation, as well as an increase in the content of antigen-antibody complexes in the bloodstream. Increased frequency of IL10 gene polymorphisms (rs1800896, rs1800872, rs1800871) was revealed in the patients with schizophrenia. A relationship between IL-6 and IL-8 levels and the carriage of IL1B T-511C (rs16944), IL10 1082A (rs1800896), IL10 592 C&amp;gt;A (rs1800872) and TLR3 Leu412Phe (G/A) (rs3775291) single nucleotide polymorphisms was found. Conclusion:&amp;nbsp;The revealed associations may indicate a role of SNPs in cytokine and Toll-like receptor genes in modulating the network genetic interactions underlying certain immunological endophenotypes in the patients. Based on the results of this work and literature data, it is important to further study the relationship of immunogenetic markers in schizophrenia with the immune profiles of the disease and its clinical manifestations, including in larger samples of patients.</p></abstract><trans-abstract xml:lang="en"><p>Background:&amp;nbsp;Schizophrenia is a multifactorial and clinically polymorphic disease with a significant hereditary component. The study of the influence of functionally significant polymorphisms of the genes regulating immune response and inflammation on the immune parameters in patients with schizophrenia is relevant for the development of new methods for predicting the course of the disease and finding new therapy targets. The aim of the study:&amp;nbsp;To study the association of polymorphisms in cytokine and Toll-like receptor genes with the serum levels of immune mediators in patients with schizophrenia. Materials and methods:&amp;nbsp;95 patients diagnosed with schizophrenia and 99 healthy volunteers were recruited into the study. Polymorphisms of genes regulating the immune response (IL1B rs1143627, IL4 rs2243250, IL2 rs2069762, IL10 (rs1800896, rs1800872, rs1800871), IFNL rs8099917, IFNL rs12979860, TLR9 rs5743836, TLR9 rs352140, TLR3 rs3775291), the serum level of major cytokines and markers of systemic inflammation were determined. Results:&amp;nbsp;The patients were found to have elevated levels of key pro-inflammatory cytokines IL-8 and IL-17A and other markers of systemic inflammation, as well as an increase in the content of antigen-antibody complexes in the bloodstream. Increased frequency of IL10 gene polymorphisms (rs1800896, rs1800872, rs1800871) was revealed in the patients with schizophrenia. A relationship between IL-6 and IL-8 levels and the carriage of IL1B T-511C (rs16944), IL10 1082A (rs1800896), IL10 592 C&amp;gt;A (rs1800872) and TLR3 Leu412Phe (G/A) (rs3775291) single nucleotide polymorphisms was found. Conclusion:&amp;nbsp;The revealed associations may indicate a role of SNPs in cytokine and Toll-like receptor genes in modulating the network genetic interactions underlying certain immunological endophenotypes in the patients. Based on the results of this work and literature data, it is important to further study the relationship of immunogenetic markers in schizophrenia with the immune profiles of the disease and its clinical manifestations, including in larger samples of patients.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>cytokines</kwd><kwd>inflammation</kwd><kwd>single nucleotide polymorphisms</kwd><kwd>schizophrenia</kwd><kwd>Toll-like receptors</kwd></kwd-group><kwd-group xml:lang="en"><kwd>cytokines</kwd><kwd>inflammation</kwd><kwd>single nucleotide polymorphisms</kwd><kwd>schizophrenia</kwd><kwd>Toll-like receptors</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>Kerage D, Sloan EK, Mattarollo SR, et al. Interaction of neurotransmitters and neurochemicals with lymphocytes. Journal of Neuroimmunology. 2019;332:99-111. DOI: https://doi.org/10.1016/j.jneuroim.2019.04.006</mixed-citation></ref><ref id="B2"><mixed-citation>Bechter K. Updating the mild encephalitis hypothesis of schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2013;42:71-91. DOI: https://doi.org/10.1016/j.pnpbp.2012.06.019</mixed-citation></ref><ref id="B3"><mixed-citation>M&amp;uuml;ller N, Krause D, Weidinger E, et al. Immunological treatment options for schizophrenia. Fortschritte der Neurologie-Psychiatrie. 2014;82(4)210-219. Deutsch. DOI: https://doi.org/10.1055/s-0033-1355776</mixed-citation></ref><ref id="B4"><mixed-citation>Goldsmith DR, Rapaport MH, Miller BJ. A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression. Molecular Psychiatry. 2016;21(12):1696-1709. DOI: https://doi.org/10.1038/mp.2016.3</mixed-citation></ref><ref id="B5"><mixed-citation>Miller BJ, Buckley P, Seabolt W, et al. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biological Psychiatry. 2011;70(7):663-671. DOI: https://doi.org/10.1016/j.biopsych.2011.04.013</mixed-citation></ref><ref id="B6"><mixed-citation>Potvin S, Stip E, Sepehry AA, et al. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biological Psychiatry. 2008;63(8):801-808. DOI: https://doi.org/10.1016/j.biopsych.2007.09.024</mixed-citation></ref><ref id="B7"><mixed-citation>Malashenkova IK, Krynskiy SA, Ogurtsov DP, et al. Immunoinflammatory profile in patients with episodic and continuous paranoid schizophrenia. Consortium Psychiatricum. 2021;2(1):19-31. DOI: https://doi.org/10.17816/CP66</mixed-citation></ref><ref id="B8"><mixed-citation>Maes M, Plaimas K, Suratanee A, et al. First Episode Psychosis and Schizophrenia Are Systemic Neuro-Immune Disorders Triggered by a Biotic Stimulus in Individuals with Reduced Immune Regulation and Neuroprotection. Cells. 2021;10(11):2929.&amp;nbsp; DOI: https://doi.org/10.3390/cells10112929</mixed-citation></ref><ref id="B9"><mixed-citation>Agerbo E, Sullivan PF, Vilhj&amp;aacute;lmsson BJ, et al. Polygenic Risk Score, Parental Socioeconomic Status, Family History of Psychiatric Disorders, and the Risk for Schizophrenia: A Danish Population-Based Study and Meta-analysis. JAMA Psychiatry. 2015;72(7):635-641. DOI: https://doi.org/10.1001/jamapsychiatry.2015.0346</mixed-citation></ref><ref id="B10"><mixed-citation>Ruzzo EK, Geschwind DH. Schizophrenia genetics complements its mechanistic understanding. Nature Neuroscience. 2016;19(4):523-525. DOI: https://doi.org/10.1038/nn.4277</mixed-citation></ref><ref id="B11"><mixed-citation>Sekar A, Bialas AR, de Rivera H, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530(7589):177-183. DOI: https://doi.org/10.1038/nature16549</mixed-citation></ref><ref id="B12"><mixed-citation>Schafer DP, Lehrman EK, Kautzman AG, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74(4):691-705. DOI: https://doi.org/10.1016/j.neuron.2012.03.026</mixed-citation></ref><ref id="B13"><mixed-citation>Dickerson F, Boronow J, Stallings C, et al. The lymphotoxin Cys13Arg polymorphism and cognitive functioning in individuals with schizophrenia. Schizophrenia Research. 2007;89(1-3):173-176. DOI: https://doi.org/10.1016/j.schres.2006.08.015</mixed-citation></ref><ref id="B14"><mixed-citation>Li X, Zhang W, Lencz T, et al. Common variants of IRF3 conferring risk of schizophrenia.&amp;nbsp;&amp;nbsp;&amp;nbsp; Journal of Psychiatric Research. 2015;64:67-73. DOI: https://doi.org/10.1016/j.jpsychires.2015.03.008</mixed-citation></ref><ref id="B15"><mixed-citation>Srinivas L, Vellichirammal NN, Alex AM, et al. Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia. Journal of Neuroinflammation. 2016;13(1):105. DOI: https://doi.org/10.1186/s12974-016-0569-8</mixed-citation></ref><ref id="B16"><mixed-citation>Garc&amp;iacute;a-Bueno B, Gass&amp;oacute; P, MacDowell KS, et al. Evidence of Activation of the Toll-like Receptor-4 Proinflammatory Pathway in Patients with Schizophrenia. Journal of Psychiatry and Neuroscience. 2016;41(3):E46-E55. DOI: https://doi.org/10.1503/jpn.150195</mixed-citation></ref><ref id="B17"><mixed-citation>Mak M, Misiak B, Frydecka D, et al. Polymorphisms in immune-inflammatory response genes and the risk of deficit schizophrenia. Schizophrenia Research. 2018;193:359-363. DOI: https://doi.org/10.1016/j.schres.2017.06.050</mixed-citation></ref><ref id="B18"><mixed-citation>Pouget JG. The Emerging Immunogenetic Architecture of Schizophrenia. Schizophrenia Bulletin. 2018;44(5):993-1004. DOI: https://doi.org/10.1093/schbul/sby038</mixed-citation></ref><ref id="B19"><mixed-citation>MacArthur J, Bowler E, Cerezo M, et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Research. 2017;45(D1):D896-D901. DOI: https://doi.org/10.1093/nar/gkw1133</mixed-citation></ref><ref id="B20"><mixed-citation>Wang Q, Yang C, Gelernter J, et al. Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS. Human Genetics. 2015;134:1195-1209. DOI: https://doi.org/10.1007/s00439-015-1596-8</mixed-citation></ref><ref id="B21"><mixed-citation>Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421-427. DOI: https://doi.org/10.1038/nature13595</mixed-citation></ref><ref id="B22"><mixed-citation>Bhati MT. Defining Psychosis: The Evolution of Schizophrenic Spectrum Disorders DSM-5. Current Psychiatry Reports. 2013;15(110):409. DOI: https://doi.org/10.1007/s11920-013-0409-9</mixed-citation></ref><ref id="B23"><mixed-citation>Ribeiro-Santos R, de Campos-Carli SM, Ferretjans R, et al. The association of cognitive performance and IL-6 levels in schizophrenia is influenced by age and antipsychotic treatment. Nordic Journal of Psychiatry. 2020;74(3):187-193. DOI: https://doi.org/10.1080/08039488.2019.1688389</mixed-citation></ref><ref id="B24"><mixed-citation>Luo Y, He H, Zhang J, et al. Changes in serum TNF-&amp;alpha;, IL-18, and IL-6 concentrations in patients with chronic schizophrenia at admission and at discharge. Comprehensive Psychiatry. 2019;90:82-87. DOI: https://doi.org/10.1016/j.comppsych.2019.01.003</mixed-citation></ref><ref id="B25"><mixed-citation>Malashenkova IK, Ushakov VL, Krynskiy SA, et al. The relationship of morphometric changes of the brain with IL-6 levels, systemic inflammation and immune disturbances in the patients with schizophrenia. Procedia Computer Science. 2021;190:553-559. DOI: https://doi.org/10.1016/j.procs.2021.06.064</mixed-citation></ref><ref id="B26"><mixed-citation>International Schizophrenia Consortium, Purcell SM, Wray NR, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature. 2009;460(7256):748-752. DOI: https://doi.org/10.1038/nature08185</mixed-citation></ref><ref id="B27"><mixed-citation>Schizophrenia Psychiatric Genome-Wide Association Study Consortium. Genome-wide association study identifies five new schizophrenia loci. Nature Genetics. 2011;43(10):969-976. DOI: https://doi.org/10.1038/ng.940</mixed-citation></ref><ref id="B28"><mixed-citation>Chen J, Liu X, Zhong Y. Interleukin-17A: The Key Cytokine in Neurodegenerative Diseases. Frontiers in Aging Neuroscience. 2020;12:566922. DOI: https://doi.org/10.3389/fnagi.2020.566922</mixed-citation></ref><ref id="B29"><mixed-citation>Chen H, Wilkins LM, Aziz N, et al. Single nucleotide polymorphisms in the human interleukin-1B gene affect transcription according to haplotype context. Human Molecular Genetics. 2006;15(4):519-529. DOI: https://doi.org/10.1093/hmg/ddi469</mixed-citation></ref><ref id="B30"><mixed-citation>Iacoviello L, Di Castelnuovo A, Gattone M, et al. Polymorphisms of the interleukin-1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:222-227. DOI: https://doi.org/10.1161/01.ATV.0000150039.60906.02</mixed-citation></ref><ref id="B31"><mixed-citation>Shirts BH, Wood J, Yolken RH, et al. Association study of IL10, IL1&amp;beta;, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: Suggestive association with rs16944 at IL1&amp;beta;. Schizophrenia Research. 2006;88(1-3):235-244. DOI: https://doi.org/10.1016/j.schres.2006.06.037</mixed-citation></ref><ref id="B32"><mixed-citation>Fatj&amp;oacute;-Vilas M, Pomarol-Clotet E, Salvador R, et al. Effect of the interleukin-1&amp;beta; gene on dorsolateral prefrontal cortex function in schizophrenia: a genetic neuroimaging study. Biological Psychiatry. 2012;72(9):758-765. DOI: https://doi.org/10.1016/j.biopsych.2012.04.035</mixed-citation></ref><ref id="B33"><mixed-citation>Papiol S, Molina V, Desco M, et al. Gray matter deficits in bipolar disorder are associated with genetic variability at interleukin-1 beta gene (2q13). Genes, Brain and Behavior. 2008;7(7):796-801. DOI: https://doi.org/10.1111/j.1601-183X.2008.00421.x</mixed-citation></ref><ref id="B34"><mixed-citation>Baune BT, Dannlowski U, Domschke K, et al. The interleukin 1 beta (IL1B) gene is associated with failure to achieve remission and impaired emotion processing in major depression. Biological Psychiatry. 2010;67(6):543-549. DOI: https://doi.org/10.1016/j.biopsych.2009.11.004</mixed-citation></ref><ref id="B35"><mixed-citation>Sasayama D, Hori H, Teraishi T, et al. Possible association between interleukin-1&amp;beta; gene and schizophrenia in a Japanese population. Behavioral and Brain Functions. 2011;7:35. DOI: https://doi.org/10.1186/1744-9081-7-35</mixed-citation></ref><ref id="B36"><mixed-citation>Chiang SS, Riedel M, Schwarz M, et al. Is T-helper type 2 shift schizophrenia-specific? Primary results from a comparison of related psychiatric disorders and healthy controls. Psychiatry and Clinical Neurosciences. 2013;67(4):228-236. DOI: https://doi.org/10.1111/pcn.12040</mixed-citation></ref><ref id="B37"><mixed-citation>Weber A, Wasiliew P, Kracht M. Interleukin-1 (IL-1) pathway. Science Signaling. 2010;3(105):cm1. DOI: https://doi.org/10.1126/scisignal.3105cm1</mixed-citation></ref><ref id="B38"><mixed-citation>Diehl S, Rinc&amp;oacute;n M. The two faces of IL-6 on Th1/Th2 differentiation. Molecular Immunology. 2002;39(9):531-6. DOI: https://doi.org/10.1016/s0161-5890(02)00210-9</mixed-citation></ref><ref id="B39"><mixed-citation>Cardona-Castro N, S&amp;aacute;nchez-Jim&amp;eacute;nez M, Rojas W, et al. IL-10 gene promoter polymorphisms and leprosy in a Colombian population sample. Biomedica. 2012;32(1):71-6. DOI: https://doi.org/10.1590/S0120-41572012000100009</mixed-citation></ref><ref id="B40"><mixed-citation>Schotte H, Schl&amp;uuml;ter B, Schmidt H, et al. Putative IL-10 Low Producer Genotypes Are Associated with a Favourable Etanercept Response in Patients with Rheumatoid Arthritis. PLoS ONE. 2015;10(6):e0130907. DOI:&amp;nbsp; https://doi.org/10.1371/journal.pone.0130907</mixed-citation></ref><ref id="B41"><mixed-citation>Enache D, Nikkheslat N, Fathalla D, et al.&amp;nbsp; Peripheral immune markers and antipsychotic non-response in psychosis. Schizophrenia Research. 2021;230:1-8. DOI: https://doi.org/10.1016/j.schres.2020.12.020</mixed-citation></ref><ref id="B42"><mixed-citation>Cho P, Gelinas L, Corbett NP, et al. Association of common single-nucleotide polymorphisms in innate immune genes with differences in TLR-induced cytokine production in neonates. Genes and Immunity. 2013;14(4):199-211. DOI: https://doi.org/10.1038/gene.2013.5</mixed-citation></ref><ref id="B43"><mixed-citation>Huik K, Avi R, Pauskar M, et al. Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users. Infection, Genetics and Evolution. 2013;20:78-82. DOI: https://doi.org/10.1016/j.meegid.2013.08.008</mixed-citation></ref><ref id="B44"><mixed-citation>Svensson A, Tunb&amp;auml;ck P, Nordstr&amp;ouml;m I, et al. Polymorphisms in Toll-like receptor 3 confer natural resistance to human herpes simplex virus type 2 infection. Journal of General Virology. 2012;93(Pt 8):1717-1724. DOI: https://doi.org/10.1099/vir.0.042572-0</mixed-citation></ref><ref id="B45"><mixed-citation>Malashenkova IK, Ushakov VL, Zakharova NV, et al. Neuro-immune aspects of schizophrenia with severe negative symptoms: new diagnostic markers of disease phenotype. Sovremennye Tehnologii v Medicine. 2021;13(6):24-35. DOI: https://doi.org/10.17691/stm2021.13.6.03</mixed-citation></ref></ref-list></back></article>