Association between anxiety and non-coding genetic variants of the galanin neuropeptide


Autoři: Gergely Keszler aff001;  Zsuzsanna Molnár aff001;  Zsolt Rónai aff001;  Mária Sasvári-Székely aff001;  Anna Székely aff002;  Eszter Kótyuk aff002
Působiště autorů: Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary aff001;  MTA‐ELTE Lendület Adaptation Research Group, Institute of Psychology, ELTE Eötvös Loránd University, Budapest, Hungary aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226228

Souhrn

Background

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.

Methods

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.

Results and conclusions

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.

Klíčová slova:

Alleles – Anxiety – Depression – DNA methylation – Emotions – Haplotypes – Linkage disequilibrium – Molecular genetics


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