Polymorphic variants of proinflammatory cytokine genes in affective disorders and in cases of comorbidity with alcohol addiction

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Abstract

Affective disorders and alcohol dependence are among the most common disorders in human population and in general medical practice. Clinical manifestations in comorbid patients with affective and addictive disorders are characterized by heterogeneity and major degree of severity. These conditions occur due to complex biological mechanisms associated with dysregulation of various neuromediator systems. The role of immunoinflammation in development of affective disorders and alcohol dependence is widely recognized, whereas participation of cytokines in pathophysiology of these disorders is still not extensively studied. The aim of the present study was to investigate polymorphic variants of genes encoding proinflammatory cytokines IL6 and tumor necrosis factor α TNFA in patients with affective disorder, and in cases of comorbid states of affective disorder and alcohol addiction. The study included 239 patients with current depressive episode within bipolar disorder, single depressive episode, recurrent depressive disorder, and with dysthymia (F31, F32, F33, F34.1, ICD-10; group F3). Another study group included 69 patients with comorbid course of alcohol dependence (F10, ICD-10) and affective disorder (group F3 + F10) compared with controls (205 mentally healthy individuals). Severity of condition and mental state of the patients was assessment in the course of therapy using SIGH-SAD, SHAPS and SASS scales. Genotyping of DNA samples for the polymorphic variants of IL6 gene marker (rs2069840) and TNFA (rs361525, rs1799964) was performed by real-time PCR technique with QuantStudio™ 5 Real-Time PCR System amplifier (Applied Biosystems, USA) using the Biomaster UDG HS-qPCR Lo-ROX (2×) kits (Biolabmix, Russia), and primers of the DNA-synthesis Company (Russia). The analysis of IL6 polymorphic variants (rs2069840) and TNFA gene (rs361525, rs1799964) showed an evidence for contribution of Т allele of TNFA rs1799964 polymorphism to development of alcohol addiction, and an association of polymorphism rs2069840 of IL6 gene with clinical degree of symptoms in depressive disorders. Our findings confirm the hypothesis about participation of cytokine-regulating gene variants in pathogenesis of affective disorders.

About the authors

Lyudmila A. Levchuk

Tomsk National Research Medical Center, Russian Academy of Sciences

Author for correspondence.
Email: levchukniipz@mail.ru
ORCID iD: 0000-0003-1982-8492
SPIN-code: 7609-2051
Scopus Author ID: 55386990200
ResearcherId: R-8201-2016

PhD (Biology), Scientific Secretary, Senior Researcher, Laboratory of Molecular Genetics and Biochemistry, Research Institute of Mental Health

Russian Federation, Tomsk

Natalia M. Vyalova

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: natarakitina@yandex.ru
ORCID iD: 0000-0001-6464-6474
SPIN-code: 3214-2623
Scopus Author ID: 36169533900
ResearcherId: F-4046-2017

PhD (Biology), Senior Researcher, Laboratory of Molecular Genetics and Biochemistry, Research Institute of Mental Health

Russian Federation, Tomsk

Ekaterina V. Mikhalitskaya

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: uzen63@mail.ru
SPIN-code: 3375-2141
Scopus Author ID: 57201483055
ResearcherId: AAT-8376-2020

PhD (Medicine), Researcher, Department of Affective States, Research Institute of Mental Health

Russian Federation, Tomsk

Diana Z. Paderina

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: osmanovadiana@mail.ru
ORCID iD: 0000-0002-5546-7316
SPIN-code: 4118-1155
Scopus Author ID: 57188558197
ResearcherId: P-1482-2017

PhD (Biology), Researcher, Laboratory of Molecular Genetics and Biochemistry, Research Institute of Mental Health

Russian Federation, Tomsk

Olga V. Roschina

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: roshchinaov@yandex.ru
ORCID iD: 0000-0002-2246-7045
SPIN-code: 3379-6963
Scopus Author ID: 57211884523
ResearcherId: J-1725-2017

PhD (Medicine), Researcher, Department of Affective States, Research Institute of Mental Health

Russian Federation, Tomsk

German G. Simutkin

Tomsk National Research Medical Center, Russian Academy of Sciences

Email: ggsimutkin@gmail.com
ORCID iD: 0000-0002-9813-3789
SPIN-code: 4372-4950
Scopus Author ID: 14028858600
ResearcherId: I-9405-2017

PhD, MD (Medicine), Leading Researcher, Department of Affective States, Research Institute of Mental Health

Russian Federation, Tomsk

Nikolay A. Bokhan

Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical University

Email: bna909@gmail.com
ORCID iD: 0000-0002-1052-855X
SPIN-code: 2419-1263
Scopus Author ID: 6506895310
ResearcherId: P-1720-2014

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Honored Scientist of the Russian Federation, Director, Research Institute of Mental Health, Tomsk National Research Medical Center, Russian Academy of Sciences; Head, Department of Psychiatry, Psychotherapy, Narcology with a Course in Medical Psychology, Siberian State Medical University

Russian Federation, Tomsk; Tomsk

Svetlana A. Ivanova

Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical University

Email: ivanovaniipz@gmail.com
ORCID iD: 0000-0001-7078-323X
SPIN-code: 5776-1365
Scopus Author ID: 36113599800
ResearcherId: С-5333-2012

PhD, MD (Medicine), Professor, Head, Laboratory of Molecular Genetics and Biochemistry, Deputy Director for Research, Research Institute of Mental Health, Tomsk National Research Medical Center, Russian Academy of Sciences; Professor, Department of Psychiatry, Psychotherapy, Narcology with a Course in Medical Psychology, Siberian State Medical University

Russian Federation, Tomsk; Tomsk

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