Abstract
Galanin, an inhibitory neuropeptide and cotransmitter has long been known to co-localize with noradrenaline and serotonin in the central nervous system. Several human studies demonstrated altered galanin expression levels in major depressive disorder and anxiety. Pharmacological modulation of galanin signaling and transgenic strategies provide further proof for the involvement of the galanin system in the pathophysiology of mood disorders. Little is known, however, on the dynamic regulation of galanin expression at the transcriptional level. The aim of the present study was to seek genetic association of non-coding single nucleotide variations in the galanin gene with anxiety and depression. Six single nucleotide polymorphisms (SNP) occurring either in the regulatory 5' or 3' flanking regions or within intronic sequences of the galanin gene have been genotyped with a high-throughput TaqMan OpenArray qPCR system in 526 healthy students (40% males). Depression and anxiety scores were obtained by filling in the Hospital Anxiety and Depression Scale (HADS) questionnaire. Data were analyzed by ANCOVA and Bonferroni correction was applied for multiple testing. Linkage disequilibrium (LD) analysis was used to map two haploblocks in the analyzed region. A single-locus and a haplotype genetic association proved to be statistically significant. In single-marker analysis, the T allele of the rs1042577 SNP within the 3' untranslated region of the galanin gene associated with greater levels of anxiety (HADS scores were 7.05±4.0 vs 6.15±.15; p = 0.000407). Haplotype analysis revealed an association of the rs948854 C_rs4432027_C allele combination with anxiety [F(1,1046) = 4.140, p = 0.042141, η2 = 0.004, power = 0.529]. Neither of these associations turned out to be gender-specific. These promoter polymorphisms are supposed to participate in epigenetic regulation of galanin expression by creating potentially methylatable CpG dinucleotides. The functional importance of the rs1042577_T allele remains to be elucidated.
Highlights
Common affective disorders such as depression and anxiety emerge against the background of perturbed monoaminergic neurotransmission
In single-marker analysis, the T allele of the rs1042577 single nucleotide polymorphisms (SNP) within the 3’ untranslated region of the galanin gene associated with greater levels of anxiety (HADS scores were 7.05±4.0 vs 6.15±.15; p = 0.000407)
A Bayesian multivariate analysis of gene factors revealed that the galanin signaling system consisting of the stress-inducible galanin gene and three heptahelical galanin receptors seems to play a seminal role in the development of depression by enhancing the vulnerability to environmental stressors [3]
Summary
Common affective disorders such as depression and anxiety emerge against the background of perturbed monoaminergic neurotransmission. Beyond the well-substantiated role of classical neurotransmitters such as norepinephrin and serotonin in the pathogenesis of mood disorders, a number of recent studies implicated coexpressed neuropeptides such as galanin, a 29 amino acid long inhibitory neurotransmitter and trophic factor [1], in anxiety and depression [2]. Intracerebroventricular administration of galanin resulted in anxiolytic-like action in rats [7], while its microinjection in rodent amygdala produced both anxiogenic [8] and anxiolytic effects [9]. Intra-dorsal hippocampal administration of galanin induced anxiogenic-like behaviours that could be attenuated with a type 2 galanin receptor antagonist [11]. Several human studies demonstrated altered galanin expression levels in major depressive disorder and anxiety. The aim of the present study was to seek genetic association of non-coding single nucleotide variations in the galanin gene with anxiety and depression
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