AUTHOR=Redenšek Sara , Kristanc Tilen , Blagus Tanja , Trošt Maja , Dolžan Vita 

TITLE=Genetic Variability of the Vitamin D Receptor Affects Susceptibility to Parkinson’s Disease and Dopaminergic Treatment Adverse Events

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=14

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.853277

DOI=10.3389/fnagi.2022.853277

ISSN=1663-4365

ABSTRACT=<p>Vitamin D is a lipid-soluble molecule and an important transcriptional regulator in many tissues and organs, including the brain. Its role has been demonstrated also in Parkinson’s disease (PD) pathogenesis. Vitamin D receptor (VDR) is responsible for the initiation of vitamin D signaling cascade. The aim of this study was to assess the associations of <italic>VDR</italic> genetic variability with PD risk and different PD-related phenotypes. We genotyped 231 well characterized PD patients and 161 healthy blood donors for six <italic>VDR</italic> single nucleotide polymorphisms, namely rs739837, rs4516035, rs11568820, rs731236, rs2228570, and rs1544410. We observed that <italic>VDR</italic> rs2228570 is associated with PD risk (<italic>p</italic> &lt; 0.001). Additionally, we observed associations of specific <italic>VDR</italic> genotypes with adverse events of dopaminergic treatment. <italic>VDR</italic> rs1544410 (GG vs. GA + AA: <italic>p</italic> = 0.005; GG vs. GA: <italic>p</italic> = 0.009) was associated with the occurrence of visual hallucinations and <italic>VDR</italic> rs739837 (TT vs. GG: <italic>p</italic> = 0.036), rs731236 (TT vs. TC + CC: <italic>p</italic> = 0.011; TT vs. TC: <italic>p</italic> = 0.028; TT vs. CC: <italic>p</italic> = 0.035), and rs1544410 (GG vs. GA: <italic>p</italic> = 0.014) with the occurrence of orthostatic hypotension. We believe that the reported study may support personalized approach to PD treatment, especially in terms of monitoring vitamin D level and vitamin D supplementation in patients with high risk <italic>VDR</italic> genotypes.</p>