The role of polymorphic variants of the contactin-associated-like protein-2 (CNTNAP2) gene in the formation of differences in anxiety levels
Background: The study of the multifactor nature of anxiety is caused by its role in multiple aspects of human development including physical and mental health, emotional sphere and social activity, education, etc. In turn, excessive anxiety can result in developing various psychopathologies including depression, suicidal and addictive behavior, thus determining its social significance. Together with the monoaminergic neurotransmission, the neurobiological mechanisms involved in synaptic plasticity and neurotrophics can cause individual differences in anxiety. The contactin associated protein-like 2 (Caspr2 encoded by the CNTNAP2 gene, 7q35) is one of the significant elements of this process. Changes in the nucleotide sequence of the CNTNAP2 gene are associated with developing several psychopathologies and affective-related phenotypes. The aim of the study: The present study is aimed at estimating the main effect of the polymorphic variants rs2530310, rs2710102 and rs10251794 of the CNTNAP2 gene and the haplotypic effect in the formation of individual variations in the level of situational and personal anxiety in mentally healthy individuals of different ethnicity aged 17-24 years. Materials and methods: State and trait anxiety were assessed with the Spielberger State-Trait Anxiety Inventory (STAI) in 523 mentally healthy individuals (75,7% of women) of different ethnicity from the Republic of Bashkortostan (mean age: 20.99 ± 3.32 years). Genotyping of the CNTNAP2 gene polymorphisms (rs2530310, rs2710102 and rs10251794) was conducted with PCR. The evaluation of the main effect of polymorphic loci and haplotypes of the CNTNAP2 gene in variations in the level of anxiety was carried out in the course of linear regression analysis (PLINK v.1.09). Results: As a result of the analysis, CNTNAP2 rs10251794 was associated with state anxiety in the total sample (β = 1.97; P = 0.002; PFDR = 0.007) and in men (β = 3.14; P = 0.011; PFDR = 0.032), while considering the additive effect of minor allele (A/A vs. A/T vs. T/T in rs10251794) and dominant effect of minor allele (A/A + A/T vs. T/T in rs10251794), which survived FDR-correction for multiple testing. Conclusion: The obtained data indicate the possible involvement of contactin associated protein-like 2 regulating synaptic plasticity and neurogenesis in individual differences in emotional control and anxiety-related traits.
Enikeeva RF, Kazantseva AV, Davydova JD, et al. The role of polymorphic variants of the contactin-associated-like protein-2 (CNTNAP2) gene in the formation of differences in anxiety levels. Research Results in Biomedicine.2020;6(1):20-36. (In Russian) DOI: 10.18413/2658-6533-2020-6-1-0-3
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The study was partially supported by the State Contract of the Ministry of Science and Education of RF (№АААА-А16-116020350032-1) and by the Russian Foundation for Basic Research (project № 17-29-02195). DNA samples for the study were provided by the IBG UFRC RAS collection “Collection of human biological materials” developed within the project № 007-030164/2.