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

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.