S.A. Erkinova - Student-specialist, Medical Department, Novosibirsk State University E-mail: sarafrozerkinova@gmail.com V.S. Kiselyov - Ph.D. (Med.), Neurosurgeon, Federal Neurosurgical Center, Novosibirsk E-mail: neuro-surgeon@yandex.ru N.V. Strelnikov - Neurosurgeon, Center Angioneurology and Neurosurgery named after Academician E.N. Meshalkin, Novosibirsk E-mail: strenik05@mail.ru K.Yu. Orlov - Ph.D. (Med.), Neurosurgeon, Head of the Neurosurgery Center, Center Angioneurology and Neurosurgery named after Academician E.N. Meshalkin, Novosibirsk E-mail: k.orlov@meshalkin.ru A.V. Dubovoy - Manager of the Department, Neurosurgeon with the Highest Degree, Federal Neurosurgical Center, Novosibirsk E-mail: dubovoy@mail.ru E.N. Voronina - Ph.D. (Biol.), Research Scientist, Institute of Chemical Biology and Fundamental Medicine, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia E-mail: voronina_l@mail.ru M.L. Filipenko - Ph.D. (Biol.), Head of the Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Siberian Division, Russian Academy of Sciences, Novosibirsk E-mail: mlfilipenko@gmail.com

Brain arteriovenous malformation (BAVM) - a congenital vascular pathology which is represented by a tangle of twisted blood vessels located in the brain. According to the modern representations, formation of AVM depends both on the factors of the external environment and on the set of independently operating or interacting internal mediators - inflammatory cy-tokins, vascular factors of growth stimulating angiogenesis and etc. The mechanisms participating in the formation, growth and rupture of AVM are completely not clear, but a number of researches indicate inflammation as the main contribution to pathogenesis. The influence of inflammation on pathogenesis of AVM is connected with the pro-inflammatory cytokins: Interleukin-1α,β (ΙL-1α and IL-1β), antagonists of the receptor IL-1 (IL1RN), IL-6, TNF-and and IL-8 that participate in stimulation of leuko-cytes, proliferation, migration of the endotelial cells and violation of angiogenesis. The aim of this study was to investigate the associations between single nucleotide polymorphisms (SNPs) in IL-1a, b, IL-6, IL-8 and risk of BAVM in the residents of the West Siberian region. The genotypes of 5 polymorphic loci in genes of cytokins were defined in the study on patients who have the AVM and in a control group without AVM. The study included 191 patients (mean age: 37,1±15,0, female/male: 124/67) with the BAVM. Magnetic resonance imaging (MRI) and cerebral angiography (CAG) confirmed it in the clinical centers of Novosibirsk. The control group consisted of 480 residents (mean age: 33±11,1, female/male: 199/281) of Novosibirsk without BAVM. Determination of polymorphic variants of genes was performed by Real Time PCR using TaqMan-competing probes. Distribution of the frequencies of genotypes for all researched SNP corresponds to Hardy-Weinberg\'s law in all created groups We didnt find significant assosiations of patients with the AVM and control group of rs1800587 Il-1A gene (OR=0.784,C.I.= [0.598-1.026], p=0.08), rs16944 IL-1b gene (OR=0.784,C.I.= [0.598-1.026], p=0.08), rs1800796 IL-6 gene (OR=0.946, C.I.= [0.620-1.442], p=0.77), rs4073 IL-8 (OR=0.987, C.I.= [0.777-1.255], p=0.92) At the same time we showed the association of -174G allele of IL-6 gene (rs1800795) with development of AVM (OR=1.309, CI=[1.026-1.671], p=0,03) at residents of the West Siberian region. The polymorphic variant of G-174C of IL-6 gene (rs1800795) is in the promoter region. Experiments in vitro have showed that the patients with the 174GG genotype have the triple augmentation of risk of intracranial bleedings in comparison with the allele C (OR=2.62, P=0.003), (1.96, p = 0.039). In some researches, it is shown that the 174GG genotype was bound to postoperative rising of the IL6 level in dis-eases of peripheric arteries and in the ischemic stroke. Thus, our result approves the data which we knew before on asso-ciation of - 174G allele of IL-6 gene with the various diseases which are connected with the disturbance of functioning of the vascular wall. Probably, it is bound to the raised production of the IL-6 among the bearers given of this allele and, re-spectively, to the intensifying of inflammatory proteolytic processes in the extracellular matrix of the vascular wall. Conclusion: The conducted study has shown that the presence of the polymorphic locus rs1800796 of IL-6 gene is asso-ciated with the development of the BAVM among West Siberians.

 

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