# Exploring the Influence of Fok1/Apa1 Polymorphic Variants on Adolescent Mental Health and Response to Vitamin D Supplementation in Embryonic Hippocampal Cell Lines

**Authors:** Giulia Gizzi, Federico Fiorani, Samuela Cataldi, Martina Mandarano, Elisa Delvecchio, Claudia Mazzeschi, Elisabetta Albi

PMC · DOI: 10.3390/genes15070913 · 2024-07-12

## TL;DR

This study explores how genetic variations in the vitamin D receptor affect adolescent mental health and response to vitamin D in cell lines.

## Contribution

The study introduces new insights into how specific VDR polymorphisms influence vitamin D3 treatment outcomes in mental health.

## Key findings

- No significant association was found between Fok1/Apa1 VDR variants and anxious/depressive symptoms in adolescents.
- Cell lines with AA (Fok1) and CC (Apa1) genotypes responded better to vitamin D3 treatment.
- Cell lines with GG (Fok1) and AA (Apa1) genotypes showed no response to vitamin D3.

## Abstract

Several single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) have been observed in association with susceptibility to various pathologies, including autism, major depression, age-related changes in cognitive functioning, and Parkinson’s and Alzheimer’s diseases. This study aimed to establish the association between Fok1/Apa1 polymorphic variants and anxious/depressive symptoms in nonclinical adolescents from central Italy, with the goal of identifying the risk of developing both symptoms. We found no significant difference in genotype distribution or dominant/recessive models of Fok1/Apa1 VDR polymorphic variants between subjects with anxious/depressive symptoms and controls. HN9.10e cell lines carrying the AA genotype for Fok1 and the CC genotype for Apa1 responded better to treatment with vitamin D3 than cell lines carrying the AG genotype for Fok1 and CA genotype for Apa1. Cell lines carrying the GG genotype for Fok1 and the AA genotype for Apa1 did not respond at all, suggesting avenues for future studies in both the general population and individuals with mental and/or neuropsychiatric disorders. These studies suggest that the level of response to vitamin D3 administered to prevent and/or treat mental or neurological disorders could depend on the polymorphic variants of the vitamin D receptor.

## Linked entities

- **Genes:** VDR (vitamin D receptor) [NCBI Gene 7421], ZNF410 (zinc finger protein 410) [NCBI Gene 57862]
- **Chemicals:** vitamin D3 (PubChem CID 5280795), doxorubicin (PubChem CID 31703)
- **Diseases:** autism (MONDO:0005260), major depression (MONDO:0002009), Parkinson’s disease (MONDO:0005180), Alzheimer’s disease (MONDO:0004975)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}, ZNF410 (zinc finger protein 410) [NCBI Gene 57862] {aka APA-1, APA1}
- **Diseases:** autism (MESH:D001321), mental and/or neuropsychiatric disorders (MESH:D001523), Parkinson's and Alzheimer's diseases (MESH:D010300), major depression (MESH:D003865), Mental Health (OMIM:603663), anxious/depressive symptoms (MESH:D003866)
- **Cell lines:** HN9.10e — Mus musculus (Mouse), Hybrid cell line (CVCL_LN31)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11276141/full.md

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Source: https://tomesphere.com/paper/PMC11276141